Sam & Dean track down changelings that are pursuing mothers and their children. A boy they protect bears a strange resemblance to Dean, which at first makes Dean uncomfortable because he once had a one-night stand with the boy's mother Lisa.

Sam is mysteriously released from Hell and seeks out his brother, trying to have a normal life. Together the brothers must join forces with their maternal grandfather, Samuel, and begin the fight anew.

After a group of young girls go missing Sam and Dean realize that a group of vampires have taken up residence in the small town. After a fight with two of the blood-suckers, Dean is bitten and turns into a vampire. Samuel tells Dean he can change him back but he’d have to get the blood of the vampire who turned him. Dean infiltrates the nest and runs into the Alpha...

Ben calls Dean and tells him Lisa is in trouble. Dean leaves Sam to investigate a case alone and rushes home to rescue Lisa, however, he’s not prepared for what meets him at the door. Meanwhile, Sam discovers the men that were murdered were all a part of a cruel practical joke played on a female co-worker who went missing.

A demon kidnaps Ben and Lisa to get to Dean. Sam and Dean are forced to join with an unlikely ally to free them.