Sam is shocked when Dean finally tells him their dad asked him to watch over Sam to save him, or if that fails kill him. Sam leaves alone to let Ash look up a same-type clairvoyant demonic victim. Ava Wilson, from Peoria, Indiana, fits that bill and looks up Sam to warn she saw his death, then leaves ridiculing him. Dean followed Sam, just in time to intervene when crazy Gordon Walker turns up, who will stop at nothing to destroy 'utterly evil' Sam. It's a testing fight for the brothers.
Sam and Dean visit the Pierpont Inn, a creepy old mansion turned failing hotel. They meet the owner, Susan, and her daughter Tyler, who are packing to move after they sell the hotel. Tyler is playing with a little girl named Maggie. The brothers notice strange items around the hotel, including an urn with a familiar pattern, dolls with their heads backwards and Susan's mother, who looks vacant and beyond terrified. When Susan finds them in her mother's room trying to talk to her, she throws them out and threatens to call the cops.
A jewelery store heist committed by an employee is linked to a mysterious bank robberies bring Sam and Dean into the chase. The weird part seems to be the fact that the suspects end up dead before even getting their hands on the money. A friendly tip points towards another shapeshifter. However, the search is interrupted by a hostage crisis.
In Providence, Rhode Island, the local Gloria kills a man claiming that an angel in a beautiful white night had chosen her for redemption and asked her to stab the sinner to accomplish God's will. Dean and Sam investigate the case and they discover that other people had been visited by the angel and committed murders. Further, the angel has appeared after the death of Father Gregory, who was murdered on the steps of his church two months ago. When Sam is visited by the angel and asked to kill a man, the skeptical and atheist Dean confronts the faith of Sam telling ...
After Sam goes missing for over a week, Dean finally receives a phone call from his brother. Dean finds Sam in a hotel room, covered in blood and suffering from the effects of a week long memory blackout. Upon investigation, the brothers find a video-tape of Sam killing another hunter in cold blood, which leads Sam to believe his dark side is taking over. When the dark side finally emerges Sam attacks Dean and continues on his hunter killing spree with his next targets being family friends Jo Harvelle and Bobby Singer.
Sam, Dean, and Bobby encounter what appears to be a dancing alien, a chainsaw killer, alligators in the sewers, and other oddities straight out of the tabloids while probing strange occurrences on a college campus. They discover all are actually the work of one college janitor, a Trickster who has the ability to conjure into reality anything he wants. Not helping matters is the brothers' slowly escalating feud which Bobby suspects is also the work of the Trickster.
Molly and her husband are driving along a long deserted highway at night when they come upon a farmer. The next thing Molly knows both the husband and the farmer have disappeared. Things get worse when the Winchesters inform Molly that the farmer is actually a highway ghost who, it seems, appears annually to claim a new victim, who happens to be Molly this time.
Sam and Dean come across werewolf activity when they investigate the death of lawyer who was believed to have been killed by a wild animal. While Dean tracks the werewolf on the outside, Sam offers to protect Madison(guest star Emmanuelle Vaugier)who is likely to be the werewolf's next target.
The Winchesters go undercover as PAs on a haunted movie set after getting wind of reports of tag teaming ghosts. The brothers deal with an asinine studio executive out to make cheap marketing stunts(guest star Gary Cole), a disenfranchised screenwriter seeking revenge for unnecessary revisions to a formally great script, and Dean's fan-boyish feelings for the leading lady.
When an old block is reopened in the Green River County Detention Center after thirty years, a fiend is released, killing the interns. Three months later, Dean and Sam are arrested during a heist to be sent to the haunted prison to help Deacon, a former friend of their father. While FBI Agent Victor Henricksen presses Dean, the public defender Mara Daniels believes the brothers are not guilty of most of the inconsistent charges against them, and helps the Winchester brothers in the end.
Dean gets attacked by a Djinn, a creature capable of warping reality. The next things he knows he's in Lawrence, Kansas, in a stable relationship with a woman named Carmen, his mother is alive and well, and he and Sam are no longer on speaking terms. When the idea of a peaceful existence begins to settle in, visions of his previous life as a hunter start appearing out of nowhere.
The Yellow Eyed Demon transports Sam, Andy, and Ava along with other "Special Children" Jake and Lily to the remains of a ghost town to initiate the first steps of his war against mankind. Dean contacts Bobby Singer, Ash, and Ellen for help in locating his brother.
Sam, Dean, and Bobby deal with the ramifications of the Gate to Hell opening, meeting the demon incarnations of the Seven Deadly Sins, while Dean is living life to the fullest in the shadow of a deal he made with the Crossroads Demon, and a mysterious blonde woman with a demon-killing knife assists Sam.
A strange death reported in the newspaper prompts Dean and Sam to find Lisa Braeden, a woman Dean had a weekend fling with about 8.75 years ago, only to find she has a son turning 8. While investigating the death in the paper along with several other mysterious recent deaths, Sam and Dean find they are chasing a Changeling, who is replacing children with it's offspring. The mysterious blond woman is back, giving Sam a cryptic message that he should look into his mother's friends.
The Winchesters are called regarding a robbery of their father's storage unit, and track down the robbers to find the item stolen is a cursed rabbit's foot, which provides great luck until lost, and once lost the previous owner dies within a week. Sam picks up the foot and has great fortune, until it is pickpocketted away by the mercenary Bela. Dean must then get it back before Sam's bad luck gets him killed. To complicate the whole situation, Gordon, from his prison home, has convinced two other hunters that Sam is pure evil and must be killed.
The Winchester boys head to Ohio to research several deaths in a small town, where sin has taken a firm foothold on the population; prostitution, adultery, alcohol abuse, murder, and suicide are all prevalent in the once quiet town. Dean has a revealing conversation with a demon possessed woman. The demon Ruby assists Bobby in restoring the Colt to it's demon-killing grandeur.
The 'Three Little Pigs' and 'Hansel and Gretel' come to life and attract Sam and Dean's attention to Maple Springs, NY, where they try to prevent 'Little Red Riding Hood', 'Cinderella', and 'Snow White' from having unhappy endings. Sam also confronts the Crossroad Demon with the newly refurbished Colt.
Strange land-locked drownings are happening and the boys head to the coast to find out why, discovering a Ghost Ship has been witnessed by each of the victims shortly before their deaths. They find that Bela is already involved, running a scam on elderly Gertrude Case, the aunt of the first victim with a crush on Sam.
Gordon Walker is out of prison and out for blood, Sam's blood, and pays Bela to reveal their location. Meanwhile, the Winchesters are hot on the trail of a vampire named Dixon, who in turn has a beef with Gordon.
Sam and Dean follow the trail of an Anti-Claus when victims are apparently pulled up the chimney never to be seen again. After a lead goes nowhere, the Winchesters learn the Anti-Claus in in fact a pair of old pagan gods who have assimilated into society and have found a new way of getting their yearly sacrifices. A flashback to Christmas Eve 1991 reveals how Sam found out for the first time what their father really did and where Dean got his gold amulet.