Nick Hendricks (Jason Bateman) arrives to his job at a wealthy financial firm at 6:00 am. He hurries into the building, briefly trades "Good Morning's" with the security guard at the front desk and waits at the elevator. Above the elevator door is a large electronic clock which reads 6:02 am. Nick makes it to his floor, runs to his cubicle and immediately gets to work. Two hours later his phone rings; his boss, Dave Harken (Kevin Spacey) wants to talk with him. Harken has been dangling a promotion over Nick's head for the past eight years, and Nick has been working 16 hour days to get it. Harken reprimands Nick for being two minutes late that morning and tells Nick that tardiness doesn't lead to promotions. Nick apologizes and he is soon offered to share a drink with Harken. Nick reluctantly accepts (due to the hour) and is shocked to see Harken fill only one glass with scotch, almost to the brim. He forces Nick to drink it all by himself. Nick coughs and sputters as he downs the drink, but does it anyway for the promotion.
Meanwhile, Dale Arbus (Charlie Day) is dropped off at work by his fiance Stacie (Lindsay Sloane). At work Dale repels constant sexual harassment by his man-eating dentist boss Julia Harris (Jennifer Aniston). She toys with Dale; tells him to have sex with her at all times of the day, and fondles her unconscious male dental patients. Dale refuses her advances, citing that he is engaged and he wouldn't want to betray his fiance.
Elsewhere, Kurt Buckman (Jason Sudeikis) loves his job. He is the acting second-in-command at Pellitt Chemicals owned by the warm and generous Jack Pellitt. Kurt is well-liked by all of Jack's employees, except for Jack's rude, spoiled and rotten son Bobby Pellitt (Colin Ferrell). Bobby frequents the company bathroom, where he snorts cocaine, and shows genuine disgust for his co-workers, especially Kurt. Jack and Kurt walk out to the parking lot, where Jack says that he hopes for Kurt to manage the company once he retires. Jack jumps into his car and suffers an immediate heart attack, killing him.
That evening all three friends meet at a local bar where they trade horror stories about their bosses. Nick says he would quit, but his promotion is in the bag. Kurt loves his job, and he's just afraid of what Bobby will do to the company now that he's in charge. Dale wishes he could find a new dentist to work for but explains that finding a job is difficult because he is a wrongfully labelled sex offender (after taking a drunken leak on a vacant playground next to a bar one night, and getting busted by the cops for indecent exposure). Nick suggests that they all look for new jobs when their childhood, and most likely to succeed, classmate Kenny Sommerfeld (PJ Byrne) wanders into the bar and explains how tough life was after losing millions while working for Lehman Brothers. Now he can't even get hired as a waiter, and the only way he earns money is performing sexual favors in the bar bathroom. The three realize that the possibility of finding new work is slim and commit to keeping their jobs.
The next morning Nick heads into work and is caught off guard by an emergency staff meeting. Nick has a feeling that the purpose of the meeting is to announce his promotion to company Vice President. It would mean more money, better hours, and more respect from Harken. Harken arrives, 15 minutes late, complains that his wife is cheating on him with every man in the neighborhood, and openly berates Nick for being a drunk before promoting himself to Nick's coveted job. Nick daydreams of throwing Harken out a window, but only ends up begging Harken for an explanation as to why he led Nick along for so many years. Harken rudely tells Nick that he likes him as his bitch and that he'll never be promoted. Nick angrily tells Harken that he will quit and get a better job elsewhere to which Harken retorts that he'll send out a fabricated letter of discouragement to every other financial firm in the country, saying that Nick is insubordinate, tardy, an alcoholic and very bad at his job. In short, Harken would blackball Nick from the industry if he decided to quit.
Kurt heads into work three hours late, after spending the morning at Jack Pellitt's funeral. Bobby teases Kurt and reveals his intentions for the company: he intends to sell it, collect the profits and retire on a tropical beach filled with hookers and cocaine. He tells Kurt to fire all the fat and disabled people starting with the obviously pregnant "Large Marge".
Dale heads into work and is called into Julia's office. She locks the door behind him and Dale is surprised to find that she is practically naked, save for a pair of panties and a lab-coat. She implores that Dale have sex with her and berates him with offensive names. Dale ignores her come-ons and explains that he has a fiance and that he would never betray her trust. Dale threatens to quit, until Julia brings up that he is a sex offender and nobody else would ever hire him. Dale storms out of the room, to Julia's delight.
That evening the three meet again. Kurt and Nick joke about their desire to kill their bosses while Dale, who is disgusted with Julia, would never consider murdering her. Dale storms out, while the other two re-enforce that the thought was simply a joke.
Dale returns to work the next morning and is surprised to see his fiance, Stacie, in Julia's office. Stacie explains that Julia called her up and offered some free dental work as a wedding gift. Dale attempts to turn down the offer, but is unable to do so without letting on to his and Julia's relationship. With Stacie passed out in the dentist's chair, Julie goads Dale into having sex with her ON TOP of Stacie. Dale refuses again, which prompts Julia to pull out an iPad filled with risque photos of Dale and Julia taken by Julia while Dale was unconscious. She threatens to show the images to Stacie unless Dale has sex with her. Dale escapes her office yet again.
That evening the three meet at Kurt's house. Dale arrives and shouts "I'm in! Let's kill this bitch!" The other two, who were both under the impression that their conversation of murder was only a joke, try to calm Dale down, but Dale is still infuriated by Julia's actions and explains that he already has a plan.
The following evening, the three meet at a run-down motel room. Dale has gone on Craigslist and hired a "Wet Work" specialist on the men-seeking-men section. Nick and Kurt are surprised that Dale not only found an assassin on Craigslist, but managed to secure his services for only $200. The Wetwork Man (Ioan Gruffudd) pulls his car into the parking lot. He is well dressed, drives an expensive European sports car, and speaks in an English accent. The Wetwork Man enters the motel room and after a moment of confusion, explains that he is no assassin, but rather a gigolo for fetishists and that "Wetwork" is a code-name for a man who urinates on other men for arousal. The three pay the man for his time, but not his services, and flee the motel.
In Kurt's car the three accuse one another of being amateurs and decide that the next course of action is to find a killer-for-hire in person. Kurt turns on his OnStar-like GPS service and is answered by an Indian phone-operator named "Gregory". Kurt asks for directions to the most dangerous part of town. Gregory leads them to a dangerous neighborhood, where they find a bar full of thugs and gang-members. Kurt asks the bartender if he knows any killers-for-hire. The three are run out of the bar by the patrons, and just before leaving they're confronted by Dean "Motherfucker" Jones (Jamie Foxx). Jones explains that he just finished a ten year stint in prison and can help take care of their problem for $30,000. The three reject his offer as too expensive, and are about to drive away when Jones lowers his asking price to $5,000. The three withdraw all of their collective savings and meet Jones the next night, and are ready to give him the addresses of their bosses. Jones changes the details of the plan, saying that instead of having him kill their bosses, the three should kill each other's bosses, and that for the low $5K fee, he will act as their murder consultant. The three are clearly upset and want their money back, but they feel threatened by Jones, and accept the arrangement. Jones gives them a few tips on killing their bosses: make their deaths look like an accident, stake out their homes, learn their daily routines, don't leave DNA evidence, etc.
The following day Nick feigns sick by throwing up in a trash can in the middle of the office. Harken, disgusted by Nick, tells him to finish his work at home and to have it ready for Monday morning. Nick then meets with Dale and Kurt and the three of them head to Bobby's house first. As Bobby leaves, the three sneak in. Despite telling one another to leave zero impact in the house, the three make a mess. Dale and Nick accidentally knock over a shoe-box full of cocaine onto the floor while Kurt rubs all of Bobby's toothbrushes, razors and floss on his butt-crack. Dale and Nick manage to vacuum up the spilt cocaine and Kurt steals Bobby's cell phone with all his schedules, addresses, etc.
The three jump into Kurt's car and head over to Harken's mansion to look for more dirt on him and to learn his routine. Dale, who is still reeling from the cocaine he inhaled is told to sit in Kurt's car and act as a lookout. Inside, Nick and Kurt look for anything they can use to kill Harken but only find that he has a thing for cats and that his wife (Julie Bowen) is much younger and more attractive than Harken, which excites the always-horny Kurt.
In Kurt's car, Dale inhales a peanut butter and jelly sandwich while he plays video games on his cell phone. Unbeknownst to him, Harken is taking his nightly walk around the neighborhood. Dale tosses his peanut better and jelly wrapper out the window. Harken lifts it up and shouts obscenities at Dale, but soon inhales a few peanut particles and goes into anaphylactic shock. Upstairs, in Harken's bedroom Nick and Kurt watch as Harken keels over in the street. Dale exits the car and not knowing that Harken is Harken, he takes Harken's epipen and repeatedly stabs him in the chest and neck. From upstairs Nick and Kurt watch in horror as Dale apparently stabs Harken to death; they both escape, but not before accidentally dropping Bobby's cell phone in the master bedroom. Eventually the shock wears off, just as Harken's wife arrives. She thanks Dale for saving Harken's life while Harken accuses Dale of being there to sleep with his wife, and threatens to kill him. Dale drives off, tracks down Nick and Kurt and the three escape, now knowing that Harken has a severe peanut allergy: something they can use to their advantage.
The following day, the three head to the supermarket. Dale loads up on peanuts and Nick buys rat poison, which he intends to mix into Bobby's cocaine. Afterward the three head in three separate directions. Dale will kill Harken, Kurt will kill Julia, and Nick will kill Bobby.
Kurt watches as Julia drives home and seductively undresses in her front window. She eats various sexually suggestive foods before inviting the woman-crazy Kurt into her home where the two have sex.
Nick watches as Bobby exits his home with a couple of hookers. He waits for the most opportune moment to sneak in and tamper with Bobby's cocaine.
Outside the Harken residence, Dale watches "The Notebook" on his DVD player and waits for Harken to emerge. Inside his mansion Harken searches for residue of any man that might have been in his room with his wife. He hears Bobby's phone ring; he picks it up, checks Bobby's address on the phone, and heads out. With Harken gone, Dale sneaks into Harken's house, up to his shower and intends to put peanuts in all of his shampoos and soap. He calls Nick, saying that he can't go through with it. Just then Harken arrives at Bobby's house; he doesn't notice Nick's car as he walks to Bobby's front door, rings the doorbell and shoots Bobby twice, killing him. Nick and Dale witness the killing and are freaking out. Shortly after Harken leaves, Nick peels out in his Prius and blows through a couple red traffic lights and is photographed by traffic light cameras.
The three head back to their hangout. Nick and Dale are freaking out while Kurt is happy and content. Nick explains that Harken killed Bobby for them, while Kurt explains that he slept with Julia. The three fear that their DNA is all over Bobby's apartment and agree that their only course of action is fleeing the country. As they head out to Kurt's car, the three are quickly arrested by the police. At the police station, the interviewing officers ask why Nick was photographed fleeing a crime scene at such a high rate of speed. Nick fibs, saying that he was drag-racing. The two officers have a hunch that the three are connected to Bobby's slaying, but don't have enough evidence to keep them at the station. As they leave, the arresting officer tells them that they're going to send crime scene examiners to Bobby's apartment. This freaks out Kurt who had playfully rubbed all of Bobby's brushes up and down his butt.
Kurt drives them back to his apartment and are shocked to see two patrol cars parked in front of it; the cops ran the DNA evidence and now there must be a warrant out for his arrest. Finding no other recourse, the three return to see "Motherfucker" Jones. They tell him about Harken murdering Bobby, and while their actions have been suspicious they haven't actually killed anybody. Jones tells them that for his advice they would need to pay him an additional $5,000. They refuse stating that the first $5K was enough. Jones breaks down, revealing that he did not go to jail for murder, but rather for video-taping "Snow Falling on Cedars" in a movie theater ten years earlier. Despite no longer having credibility, Jones tells them to get Harken to confess to the crime and to record it. The three agree that this is the best course of action.
They sneak back into Harken's house, with Kurt manning a tape recorder and are surprised as a few dozen people, including Harken's wife jump out shouting "Happy Birthday!" They soon realize that the three are not Harken. Harken's wife recognizes Dale and assumes that during the prior meeting that she must have invited Dale to the party. The three make their way into the crowd and wait for Harken to arrive. Harken arrives soon thereafter and is annoyed by the surprise birthday party. He heads into his private office and is followed by Dale and Nick while the ever-horny Kurt sneaks off with Harken's wife.
In his home office, Nick and Dale confront the psychopath Harken. They successfully goad him into confessing for Bobby's murder, which excites them both, until they realize that Kurt, and the tape recorder, are not in the room. Harken walks over to his safe, takes out his revolver and tells them that he will kill them next. The three regroup and head out to Kurt's car. Harken jumps into his SUV and heads after them. Harken crashes into them repeatedly, prompting Kurt's Onstar-esque service to alert him. "Gregory" asks if they need assistance, to which Kurt says 'yes'. Gregory calls the police, making the three freak-out. They tell him not to call the police because they're already wanted by the cops. Hearing this, Gregory remote-shuts off the car, explaining that he is required by law to not aid fleeing fugitives. The three are soon broad-sided by Harken's SUV. Harken steps out, with his gun drawn, and orders the three to get out of the car. He explains that he would love to kill them, like he did Bobby, but he would rather frame them for Bobby's murder. He shoots himself in the leg, wipes his prints and tosses the gun to Dale, who stupidly catches it bare-handed and waits for the police to arrive. Once they arrive Dale drops the gun and Harken tells his falsified story to the same arresting officers as before. In the midst of the stories, Kurt reveals that his tape recorder must've been recording the whole time. He pulls it out and plays it aloud for all to listen. Instead of Harken's confession he plays the mistakenly recorded sounds of him and Harken's wife having sex in Harken's bathroom, followed by the sound of the car chase, but no confession. Harken laughs it off, telling the officers to arrest them as there is no confession. "Gregory" chimes in from Kurt's car and explains that he had been monitoring and recording Kurt's call ever since the first collision of the car chase. He plays back Harken's confession. Harken is soon cuffed, along with the others, and is dragged to jail.
In the epilogue, Harken has just been sentenced to 25-to-life in prison. In his absence Nick has been promoted to Harken's job as President of the company. He arrives to work at a reasonable hour and has nothing but good things to say about his new boss, Company CEO Lou Sherman (Bob Newhart) who isn't nearly as domineering or aggressive as Harken was; that is until Nick hears the pleas of Lou's assistant trapped in his trunk.
Kurt returns to his regular job at the Chemical Company where "Large Marge" has taken over Bobby's position. He playfully jokes with her, asking when her due date is, causing her to ask "Due Date?" (She's fat, not pregnant)
However in the final scene, Dale is back at work at the nasty Julia's office as usual and on this day he's finally agreed to fulfill her nasty fantasies. He tells her that he's sedated the patient in the dentist's chair and that he wants to watch her fondle the patient. She immediately pulls the patients pants down and is about to do more when the patient begins to giggle. The patient pulls back the oxygen mask revealing himself to be Kenny Sommerfeld, who is delighted to be making a buck in such a naughty situation. More so Dale has Julia look out the window where she sees video-pirate "Motherfucker" Jones video-taping her encounter. Dale blackmails Julia, explaining that in exchange for keeping the video secret he will require an all-expenses paid two week honeymoon vacation and no more sexual advances in the office. Overpowered, Julia agrees.
During the closing credits there is a blooper reel of various scenes throughout the movie.