After arguing about the search for their father, Sam and Dean split ways - Sam to continue the search in California, Dean to hunt the mysterious disappearances of passing-through couples in Indiana.
After Dean is fatally injured on a case, Sam thinks he's found a cure in a preacher who performs miracles. However, after they discover that these miracles are not as 'holy' as advertised, the brothers race to stop them before another innocent life is sacrificed.
When Sam's visions start happening while he's awake, he and Dean investigate the unusual murders he foretold only to find them all to be true. And that perhaps he's not the only one with special abilities.When visiting the Millers the boys go as priests.
After following a history of disappearances in Hibbing, Minnesota, Sam finds himself locked in a cage and Dean must team up with a by the book sheriff to find him......before the hunt begins.
While looking into a mysterious murder in Illinois, Sam and Dean come across Meg, an old 'friend' of Sam's, who may be far worse than they ever thought possible and who plans to use the brothers as bait to trap their father, John.
When a case of a seemingly average haunting begins to go haywire, Sam and Dean come to find that two bumbling, wanna-be paranormal investigators, Harry and Ed, are already on the case.
Dean gets a second chance to right a wrong from his past when the brothers get a mysterious tip from their father about a case they'd worked years ago, but left unfinished after Sam was nearly killed by the creature.
When two sets of owners of the same painting are brutally murdered, Sam and Dean investigate with the help of an auction house owner's daughter, all while Dean shamelessly tries to pair her with his little brother.
After John's mentor, a vampire hunter, is murdered, John shows up to help his sons solve the case. The vampires have taken an antique gun with supernatural powers. The Winchesters set out to retrieve the gun.
Meg turns to killing John's friends in order to get the Colt. Sam and Dean stakeout the Demon's next target; a family with a six month old baby showing signs of special abilities. John heads off alone to confront Meg.
In the aftermath of the car crash, the surviving Winchesters go to the hospital, where one is stalked by a Reaper while another must consider sacrificing himself to save the others.
After the events at the hospital, the brothers have no idea where the demon that killed their mother is hiding. While biding their time trying to come up with an idea, they investigate murders committed by a killer clown.
Dean and Sam investigate the death of a young college student who died in a car accident, but whose grave is now surrounded by a circle of dead plants.
Sam and Dean meet Andy Gallagher, a slacker with psychic powers of persuasion. Once the brothers learn that Andy's family was visited by the Demon, Sam wonders if he could be one of the special children.
Sam and Dean meet up with America's first serial killer, while Jo lies to her mother about going to Vegas and joins Sam and Dean to help them on their hunt.
Sam has a vision of Dean shooting a defenseless man, and they go to the town of River Grove, where they find the townspeople have been possessed by a virus that makes them violent.