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.

Dean seeks out Death to help get Sam's soul back. Death tells Dean he will help Sam if Dean will agree to act as Death for 24 hours. Meanwhile, Sam decides he doesn't want his soul back and asks Balthazar for a protective spell to keep his soul out of his body. Balthazar tells Sam he needs the blood of his father for the spell to work and since John Winchester is dead, Sam decides Bobby is the next best thing.

Dean and Sam find themselves in an alternate reality where everyone believes they are two actors named Jensen Ackles and Jared Padalecki, who star in a TV show called Supernatural about two brothers who hunt monsters.

After Balthazar changes history and keeps the Titanic from sinking, Fate intervenes and begins killing those that would have died on the ship. Castiel tells Sam and Dean that Fate is very upset with the two of them and the only way they can stay alive is to kill her.

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 to help him and are forced to stand by and do nothing while Sam breaks. The battle for heaven comes to a head.