Sam and Dean must find a way to escape from a government-run detention facility; in an effort to find her sons, Mary and Castiel seek assistance from a surprising source.
Mary asks Sam, Dean and Castiel for help on a case she's working, but neglects to mention the British Men of Letters are involved. When Mary is double crossed, everything is revealed.
Sam and Dean investigate an attack by an invisible hellhound at a campsite. Meanwhile, two of Crowley's own personal demons uncover what he has been hiding. Elsewhere, Castiel gets a lead on Kelly Kline.
Dean and Sam let Mick Davies tag along on a case as they search for a werewolf and they run into Claire Novak, the reunion is short lived after Claire is bitten and the brothers race to find a way to help her before she turns.
Sam comes up with a way to stop Lucifer's baby, but Castiel has something else in mind for Kelly. Dean is furious when he finds out someone stole the Colt.
Sam and Dean are alarmed when they learn hunters are being killed by suspicious "accidents" all over the country. They decide it is best to find Mary and make sure she's safe. Meanwhile, Toni is back in the states and she and Mary face off.
Sam and Dean only have each other to rely on when they're caught in a dangerous situation; the fight between the American hunters and the British hunters comes to a head.
A wraith kills her friend and Missouri enlists the help of Dean and Jody to protect her granddaughter, Patience, and could be next on the wraith's hit list. Sam continues to work with Jack to control his powers.
When multiple patients of grief counselor Mia Vallens turn up dead, Dean, Sam and Jack investigate the mystery surrounding the murders and, each inadvertently, are forced to deal with unresolved grief of their own.
Sam and Dean work on a case involving the ghost of a demented doctor; they get assistance from an unexpected source; Castiel finds his way back to the Winchesters.
Castiel is reunited with Jack and together with Sam and Dean, they head to a sleepy old western town to investigate a murder. Dean gets to live out his boyhood fantasy when he comes face to face with a famous, gun-slinging outlaw.
As Dean and Sam continue their search for Jack, they stumble across a familiar foe; Lucifer manages to escape Michael's grasp and finds an unlikely and mostly unwilling ally.