It's a year later and Dean has given up hunting and is living with Lisa and her son Ben. Mysteriously freed from his cage in hell, Sam finds Dean and tells him he need to rejoin the fight and introduces Dean to a world - a family - he never even knew existed: the Campbells, his mother's family, lead by none other than their Grandfather Samuel.

Sam turns to Dean for help when he's forced to take in the baby of parents murdered by shapeshifters. However, the brothers realize they have more problems when they discover that the baby is a shapeshifter... and it's father will stop at nothing to recover it.

Sam and Dean call Castiel for help when they investigate a case about several dead police officers who seem to have been killed by the plagues of Egypt. Castiel confirms the staff of Moses was used to kill the cops and tells Sam and Dean that Heaven is in a state of chaos and God's weapons have been stolen. The three head off to find the thief and come face to face with an old enemy.T

It's several days in the life of Bobby Singer, when he tries to recover his soul from the demon Crowley, deal with Sam and Dean's personal issues, cope with an outbreak of international monsters, handle a local woman with a crush, and get a piece of peach cobbler.

While investigating a series of murders caused by vampires, one of them feeds Dean his blood. While Dean tries to fight off the compulsion to feed on humans, Samuel arrives with a cure... but it will require the blood of the vampire that converted him.

When several people kill themselves after asking for the truth, Sam and Dean investigate and realize that Veritas, an ancient goddess of truth, has been summoned. Her victims die when the hear more truth than they can stand. However, when Dean is cursed, he decides to take advantage of the situation to ask Sam a few questions.

Castiel confirms what has happened to Sam, and the brothers go to Samuel for answers. He's busy leading a hunt against the Alpha Vampire, and the Winchesters insist on going. However, the hunt goes horribly awry, and Dean and Sam learn what Samuel is up to.

Dean and Sam investigate what seems to be a werewolf killing but turns out to be a skinwalker posing as a family dog who is taking revenge on his owner's enemies. After capturing the dog, he turns human and tells Sam and Dean that an Alpha skinwalker has created many sleeper cells that will rise on his command and kill their families. The only way to stop the mass murders is to find and kill the Alpha.

While Sam and Dean are investigating a UFO sighting, Dean is abducted from a crop circle. However, when he awakens, he discovers he isn't dealing with aliens, but fairies! Unfortunately, only Dean can see the fairy that keeps attacking him which makes tracing and stopping them difficult.

Meg kidnaps the Winchesters, who offer her deal: they'll help her destroy Crowley, the new lord of Hell. In return, she'll torture Crowley for the information on Sam's soul. The brothers turn to Castiel and Samuel for help, but neither one is enthused at the plan.

Dean decides to bargain with Death to get Sam's soul back, and has to accept a wager. Meanwhile, Sam refuses to take the risk of getting his damaged soul back, and prepares to cast a spell to prevent Dean's efforts... a spell that requires the blood of someone who has been like a father to him.

Sam emerges from his coma and discovers that he remembers nothing since losing his soul. Dean and Bobby try to keep the secret, and the brothers head to Oregon to investigate the disappearance of several local female virgins. However, they soon discover that something far more sinister is involved.

Sam is lured back to a Rhode Island town where he and Samuel handled a case a year ago... and the monster is still at large, seeking revenge.

The brothers investigate two murders that appear to have been committed by haunted mannequins. As they try to save a third potential victim, Ben calls Dean and says that they have an emergency at home and Lisa is in danger. Dean takes off, leaving Sam to discover the ghost's identity.

Raphael launches an attack on Castiel and his allies, sending a particularly frightening angelic hitman after Balthazar, Sam, and Dean. In an effort to protect the brothers, Balthazar sends them to an alternate universe where they are the stars of a TV show called Supernatural and they are actors named "Jensen Ackles" and "Jared Padalecki." The brothers are confused when Castiel appears to be a tweet-happy actor named Misha Collins and Sam is married to Ruby.

Eve, the Mother of All, unleashes a new monster upon the world: a black worm-slug that can enter the brain and force people to kill. Sam and Dean join forces with Bobby and Rufus and track it to a cannery, only to discover that Gwen and Samuel are also there looking for the monster... and none of them know who the monster is inside.

In the seventeenth episode of season six (s6e17) of TV show SUPERNATURAL, the viewers can revisit the titanic tale. What happens is that Balthazar alters history and stops titanic from sinking into the sea. But fate intervenes and makes the same people die who were actually killed in the mishap. The brothers now have to kill fate to save themselves.

In the eighteenth episode of season six (s6e18) of TV show SUPERNATURAL, the brothers in their efforts to find any way to defeat Eve, find out something about the colt of Samuel. They urge Castiel to transport them back in time so that they may meet Samuel. While Dean is excited to travel in the past, Sam does not want so.

In the nineteenth episode of season six (s6e19) of TV show SUPERNATURAL, the two brothers along with Castiel and Bobby find out that Eve is in a town in Oregon. They go there and find out that the people of the town have been converted into demons but are dying. Later they meet Eve who brings the demon in the garb of the dead mother of the Winchesters.

Castiel tells Sam, Dean, and Bobby about the war in Heaven and how he and Raphael became enemies. Bobby believes Castiel is hiding something, but Dean refuses to believe it.

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

The wall comes down in Sam's head and all hell breaks loose. Dean and Bobby are, for once, at a total loss on how help him and are forced to stand by and do nothing while Sam breaks. The battle for Heaven comes to a head.