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.
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.
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 Daniel Elkins, a vampire hunter and John's mentor, is murdered, Sam and Dean are surprised when John himself shows up to solve the case. John discovers the vampires have taken an antique gun, which has the power to kill all supernatural beings. The Winchester family sets out to retrieve the gun from the vampires so they can use it to kill the demon that took Sam and Dean's mother.
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.
Sam and Dean listen to a message on John's cell phone from a woman named Ellen (guest star Samantha Ferris)and decide to track her down. They are shocked to discover Ellen runs a road house that also serves as a gathering place for hunters like themselves. Meanwhile, at a small town carnival, a demonic clown is persuading children to let it into their home so he can murder their parents.
The Winchester brothers enjoy Dean's new baby: a shiny newly restored car, while checking out a report of two recent human deaths and over a dozen split-open cows in the small town of Red Lodge, Montana. The local sheriff laughs at Sam and Dean's idea that a cult is behind it, claiming it happens naturally in the sun. But when Sam and Dean sneak into the morgue under false pretenses, they find a victim that has retractable vampire fangs. They catch demon hunter Gordon Walker, who claims to be a friend of their late father and having made both kills after six months of...
Dean and Sam assist Neil Levine, a heartbroken college kid who consoles his long-time crush after her breakup and then loses her in a car accident. Determined to have his feelings returned, Neil uses necromancy to bring her back from the dead. His efforts backfire when she returns as an angry and vengeful Zombie, forcing the brothers to stop her after she kills her boyfriend Matt and the girl he cheated on her with.
Visions show Sam, still hunting for the master demon with Dean, the way to another small town where paranormal events occur, some innocent, some chillingly evil. The Winchester brothers are convinced it's all the paranormal work of 23-year-old Andy Gallagher, but doubt as that boy, although a bit of an outcast loser living in a van filled with philosophy as well as rock music seems sincerely surprised and using his powers with self-control. Soon they find after rescuing Tracy from what seems his work there is another at least as able and less scrupled, in fact, Andy's...
Another one of Sam's visions in which Dean kills a man by name of Duane Tanner sends the Winchesters to Rivergrove, a near ghost town facing mass demonic possession. Sam and Dean begin to believe that the demons are trying to destroy the town from the inside out when the remaining town-folk try to kill them.