The film opens with several images of three young women. The images date further and further back until ending in the late 18th century.
In a private airplane, the people and the pilots are dead. The only survivors, three young women, are the obvious killers. The leader of these women finds an air-hostess still alive. After examining her eyes, she breaks her neck and the women jump out of the plane, allowing it to crash into Berlin, Germany.
The next day, somewhere in Berlin, a young 18-year-old drug addict and petty criminal, Lena, lurks near an ATM cash dispenser. Just as her victim has used the machine she pickpockets his credit card only for the victim to be arrested by the police. A police officer, Tom, chases after her and eventually catches up with her on a bridge. After a short conversation, he tries to arrest her but Lena hits him in the face, kicks him between the legs and jumps off the bridge onto a passing boat. Lena returns to her home, a large high-rise apartment block where she lives with her drug-addicted, alcoholic mother who is flirting with her parole officer.
Later that evening, Lena goes to a nightclub. Everyone in line for the club is being examined with a hidden camera by one of the women from the beginning, Louise. Upon seeing Lena, she orders the guard to let her in. Inside the club, Louise dances with Lena and offers her a drink. She asks where Lena's friends are, but Lena replies she does not have any. When Lena goes to the bathroom, Louise follows and bites her on her neck. Freaked out and seeing that Louise casts no reflection in the mirror, the terrified Lena runs home. When she awakes in the morning, the sun burns her, forcing her to stay inside. That night, Lena returns to the club to confront Louise about what has happened. She meets Louise's two companions, the silent brunette Charlotte and the cheerful redhead Nora. Although the word is never said in the film, it becomes clear that Louise, Charlotte and Nora are vampires.
The girls sell the angry and confused Lena to a Russian pimp as a prostitute. Louise plans for Lena to kill the wicked man to ease her transformation. Lena is locked in a room. When the pimp comes in to rape her, she is overwhelmed by vampiric blood lust and attacks the pimp. In the struggle, she stabs him with a broken light bulb and tries to escape but another pimp shoots her with a shotgun. The three other vampire girls return to kill the pimps before setting them ablaze. They fail to notice one mobster hiding in fear. Before leaving, Nora steals one of the mobster's Lamborghini.
When Lena awakes at the hotel, Louise gives her a glass of what appears to be blood. As Lena drinks, she feels her strength return. Louise takes care of Lena, removing her dirty and torn clothes and showing her to a bathroom where a bath is waiting. After closing the door for some privacy, Louise tells Lena the story of how she was changed 280 years ago at a masked ball. At first she hated her maker (a woman), but grew to love her after traveling throughout Europe and getting to know all the benefits of vampire life. After her maker was burned (killed by sunlight), Louise wanted to commit suicide to join her, but instead began searching for a new companion. Louise then settled with and turned Charlotte and Nora as her two new companions/lovers. As Lena bathes, her short hair grows and returns to its natural color, her ear and nose piercings fall out and she loses all scars, bruises and wounds (including a tattoo on her belly).
Now fully embracing her new life as a vampire (mostly due to finally leaving her life of poverty behind her), Lena spends a night shopping, partying and having fun with her three new vampire girlfriends who give her the stolen Lamborghini as a gift. As they party, Lena notices that Charlotte longingly staring at a pair of baby shoes. Charlotte also exhibits several signs of depression and engages in acts of self-harm, among other things burning her own eyeball (which immediately heals).
During a dinner at a local restaurant, (the vampires can eat and taste food, but it does not satisfy them), Louise tells Lena that there are no male vampires currently in existence, because as the male vampires grew arrogant, the females grew tired of their superiority and killed all of them with the common promise to never turn a man into a vampire. Nora also reveals to Lena that she first met Louise at a Gay Pride Love Parade of 1997 where, after a one-night stand, Louise bit and turned her. As the night comes to an end, the four vampires return to their hotel to perform their morning ritual: allowing the first rays of sun burn their skin but retreating inside before any lasting harm can be done. Charlotte stays outside longer than the others, but retreats before catching fire. As they settle into their individual coffins for the day, Louise deeply and passionately kisses Lena, which startles and confuses Lena who bites Louise's lip in response. Louise interrupts herself and goes to her own coffin, where she begins cursing her hastiness.
Meanwhile, Tom uses a file on Lena to find her home address. The next night, Lena returns home to visit her mother who has not even noticed her absence. As Lena leaves after saying goodbye to her mother, Tom sees her, but almost does not recognize her due to her different color hairstyle and new fancy clothing. He tells Lena that she could go to prison for violating her 18-month probation for auto theft if he arrested her for stealing the credit card, but says he won't because her victim (Wasja) used women. The two have coffee and talk, but when Lena suddenly sees Louise approaching, she uses her Lamborghini to retreat to the vampire's nightclub.
At the club, Lena finds Charlotte in a private room where Charlotte (finally speaking for the first time) tells Lena that she was a silent movie actress in the 1920s and that she had a husband and daughter. However, Charlotte was ashamed at herself for she was a closeted lesbian in denial of her sexuality until she first met Louise who turned and encouraged Charlotte to abandon her family to settle with her new life. Louise enters the room and asks Lena why she is acting different. Lena lies that she misses the sun, so Louise takes the girls to an indoor swimming pool area called Tropical Islands Resort that has artificial sunlight allowing them to have a pool party "in the sun". Two night watchmen find the girls and ask how they managed to get inside. Nora convinces the men to join them in the pool where she quickly kills off one of them, but as water slows the vampires down, the other tries to escape. Charlotte kills this man in a sadistic manner, slicing his throat with a piece of paper which causes him to die slowly and painfully. Lena flees the scene in terror.
Meanwhile, Tom and his partner, Lummer, interrogate the surviving Russian mobster van Gough who says that "the devil" killed his friends and stole his Lamborghini. As van Gogh describes it Tom realizes that the stolen car is the car he saw Lena drive.
Nora awakes with a bellboy she had flirted with (making it known that Nora is actually bisexual). She tries to wake him, but realizes she killed him when they had sex. Nora breaks down in tears as the other girls come into the room. Louise shows her that the SEK (German SWAT unit) is invading the building. Charlotte says she will stall them while the girls make their escape. The vampires have special cars with tinted windows to protect them from sunlight if they ever had to escape during daylight. Lena and Louise take one car while Nora drives alone. The police, who think the girls are simply dangerous criminals, are slaughtered by Charlotte. Tom enters the room looking for Lena and manages to shoot Charlotte before she attacks him, causing her to fall out the window and to the ground. As the sun starts to burn her skin, Lena and Louise manage to get her inside their car. Nora crashes into a car and is thrown into sunlight. Police open fire at the other car letting in sunlight on the vampires. Unable to save Nora, they drive away as Charlotte looks back at Nora burning to death and screaming in agony. The roof of the car is ripped off by a roadblock and the girls crash into a subway to escape the scourging sunlight.
The three remaining vampire girls (Lena, Charlotte and Louise) hide at the abandoned Teufelsberg (The Devil's Mountain) where Louise has kept cash. Louise angrily blames Lena for leading the police to them and for Nora's death. Now wanted by the police, the girls prepare to escape to Moscow to make their new home there. Before leaving, Charlotte demands to see her elderly daughter.
At a local retirement home, Charlotte sings a lullaby to her dying daughter whom in her last moments recognizes her mother. With a whole day before their departure flight to Russia, the girls return to their hideout to perform their morning ritual. As the sun rises, Charlotte locks Lena and Louise inside and allows the sun to kill her. Louise screams at Charlotte to open the door as she and Lena break down into tears as they hear Charlotte's dying screams.
Lena goes to Tom to say good bye and show him who she really is (She forces him to shoot her and the wound heals in front of his eyes). Lena begins to cry while Tom holds her and they fall asleep. Lummer, who has suspected Tom of having some involvement with the girl since the hotel attack, has the SEK invade the building. Lena almost kills the policemen but is stopped by Tom's plea, leading to their arrest and incarceration.
Louise goes to the watchmen while they're in the shower and kills them (director Dennis Gansel plays one of the cops getting killed). After that she asks Lena how she will manage to live with Tom, a human, because he will die in 60 years or less while she will never age and then she'll be alone. Louise kidnaps Tom, and Lena follows her. The sun is rising when they meet and Louise finally says to Lena, "I love you". Lena (who is really straight) tells Louise that she lovers her back. Louise says that that's the most beautiful lie she's ever heard and shoots Tom. Louise and Lena have a fight and Lena throws Louise out a window into the sunlight, where she dies with a peaceful smile on her face. Lena runs to the wounded Tom and wants to bite him to make him a vampire like her so they can live together forever, but stops, kisses him and begins to cry.
In the final scene, the SEK arrives with Lummer. Lena and Tom are both gone with no trace other than Louise's gun. Lummer looks outside and sees something the other policemen and the audience don't. Lummer whispers "good luck" and walks away from the scene.