Sam's gone missing. Dean has been searching everywhere for him until suddenly he receives a phone call from Sam. He finds him sitting in a motel room with blood all over him and no memory of how he got there or of anything from the previous week. They try and retrace Sam's movements for missing time and discover a car with more blood in it and a nasty looking knife. Wiping any fingerprints, just in case, Sam finds a gas receipt in the car, so they continue along the trail. The clerk in the gas station clearly remembers him - shouting that Sam is banned after coming in drunk and attacking him the previous day. He tells Dean that he saw Sam leave and head north on Route 71.
Heading down the road, Sam suddenly tells Dean to turn down a specific road and they come across a house. When no-one answers, they sneak in and discover a dead body on the floor. Sam is convinced that he must have killed the man, even though he doesn't understand why and they discover that the man is a hunter. The man, Steve Wandell, has a CCTV set up in the house and they watch the video tapes, clearly seeing Sam kill him.
They clean up the evidence of them being there and leave. Sam believes he is turning evil - he confides in Dean that he is experiencing serious feelings of rage and hate - he thinks this is a sign of him turning into whatever he thinks he's destined to be. He asks Dean to kill him, but obviously Dean refuses. Sam is scared he might hurt Dean, but Dean assures him that whatever is wrong, they'll fix it.
Sam picks up the gun and hits Dean with it, knocking him out.
Hammering on the door wakes Dean up and the motel owner reveals that Sam left before dawn in the Impala. Dean attempts to track Sam via the GPS in his cellphone. He tracks him to Duluth, Minnesota.
Sam arrives in Duluth and walks into a bar where Jo Harvelle is working. They talk about what happened between their fathers and suddenly Sam grabs and attacks her. He knocks her out and when she wakes up, she is tied up and Sam taunts her about the death of her father, telling her she is being used as bait. Dean turns up and Sam begs him again to shoot him. Again, Dean refuses, even though Sam is threatening to hurt Jo.
Dean flings holy water at Sam, realizing what is happening and exposes the demon that was possessing Sam. Sam takes off and Dean follows. The demon reveals that he is planning to kill as many hunters as he can find. Sam shoots Dean in the shoulder, knocking him into the water. Jo finds him and takes him back to the bar to pull the bullet out of him. Jo wants to follow Dean and help him find Sam, but he wont allow her to follow.
Sam knocks on a door and their old friend Bobby answers. Bobby offers Sam a beer, which he drinks and is suddenly consumed in agony; Bobby spiked his beer with Holy Water. Bobby quickly knocks him out and traps him under the Key of Solomon. Dean arrives at the scrapyard and starts flinging holy water at the demon. Bobby starts the exorcism while Dean keeps trying to demand more information from the demon. The demon reveals that he doesn't care about any larger master plan; he just wants revenge on the hunters. The exorcism fails and Bobby discovers a binding link; the demon has bound himself to Sam. He fights back and manages to free himself, attacking Dean. He reveals that he was the same demon who had possessed Meg.
Bobby burns Sam's arm, destroying the binding link and exorcising the demon. Sam has no recollection of anything that has happened. Bobby tells them that Steve Wandell has been found dead and warns the brothers to keep out of the way. He also offers the boys protection charms to prevent any future possessions.