Sheriff Jody Mills befriends a young girl on the run from vampires. When she's forced to kill one of the monsters, Jody calls in Sam and Dean for help. However, they discover that everything isn't at it seems.

Sam learns that former Men of Letters, Magnus, once built a magical box and Sam sets out to find it in the hopes it can cure Dean of the Mark of Cain. However, what he’s not prepared for is the deadly alarm system Magnus set up on the box. When Sam opens the box, he puts both his and Dean’s life in danger.

Sam and Dean drop in on Jody Mills, Claire and Alex after receiving a panicked phone call from Claire. She believes the recent murders in town are supernatural and wants the boys’ help. However, Sheriff Mills tells Sam and Dean that Claire has been getting into trouble lately as she’s been attacking normal people and accusing them of being monsters.

A dangerous creature is accidentally released into an old house, attacking a mother and her child and leaving them both in a coma. Sam and Dean learn that Bobby and Rufus once tracked the same creature, so the Winchesters look to the past to come up with a plan to catch the monster.