A sleep-deprived Sam is running through the night, Lucifer’s voice echoing in his head. He finally finds a drug dealer who offers him something to doze off. Sam goes back to his car and tries to doze off, but Lucifer continues to keep him up despite the drug’s influence. After being woken up, Sam staggers into the street and is hit by a car.
When Dean hears about the incident, he goes to the hospital where Sam has been admitted and demands to see his brother. The physician in charge, Dr. Kadinsky, explains that Sam has had a psychotic breakdown and has been locked up for his own good. Kadinsky takes Dean to see Sam and explains that he is resisting the sedatives. Dean tries to talk to Sam, who is still seeing Lucifer, and promises that he’ll find him help. Sam tells him not to put him through the agony since they’ve discovered before that there aren’t any authentic healers and there’s no point in Dean looking.
Back at the motel, Dean starts calling all of the likely leads in Bobby’s address book. As he takes a break to get a beer, a wind blows out of nowhere, knocks the address book to the ground, and a business card for Mackey’s Taxidermy falls out. Dean contemplates the card and then leaves a message for the hunter, Mackey.
Lucifer continues to torment Sam, taking the form of Kadinsky and threatening to torture him. As Sam tries to eat, he sees maggots in his food and throws it to the floor in disgust. When he looks up, he sees a young female patient with bandaged burns watching him. After a moment studying Sam, the patient walks away.
Mackey calls Dean back and tells him that he’s been tracking a man named Emanuel Allen who has a reputation as a healer. The hunter called Emanuel’s wife, Daphne, and asked Emanuel to visit him. The healer came, and all of Mackey’s traps and tests did nothing against him. Further, Emanuel cured Mackey’s injured eye, and the hunter tells Dean that the healer is real.
The patient, Marin, comes back to see Sam and offers him a candy bar.
Dean goes to the Allen home and a man at the door greets him. He says that Daphne is indisposed, but then he shows black eyes, revealing that he’s a demon. Dean warns him that Crowley wants the Winchesters alive, but the demon warns him that Crowley doesn’t see a point in keeping the Winchesters alive if they can’t take out the Leviathans. He attacks Dean, who kills him with the demon-killing knife, and Dean turns to see that Emanuel has just arrived... and looks like Castiel.
Castiel, able to see the demon for what he really is, wonders what is going on. He goes inside with Dean and they rescue Daphne, who the demon tied up. Dean doesn’t tell Castiel who he really is, and explains that demons exist and there are a lot more out there. Once he gets through explaining, Dean asks Castiel to help Sam.
At the psych ward, Lucifer continues to gloat over Sam as he’s unable to sleep. The orderly, Marcus, comes in with food but refuses to say anything about Marin except that she wasn’t brought in because of an accident.
As Dean drives Castiel to the hospital, he asks how Castiel and Daphne met. Castiel explains that Daphne was hiking and found him in the forest, naked and suffering from amnesia. She insisted that God led her to Castiel. When Dean wonders if he has any memories of his previous life, suggesting he might have been a bad person, Castiel assures him that he doesn’t feel like a bad person.
As Sam struggles to stay awake, Marin visits him again, giving him another stolen candy bar. He invites her to stay and she explains that she’s been there for five weeks. When he asks her about the bandages, Marin says that she’s been feeling suicidal and just wants everything to be over. Sam asks her why and Marin says that there’s a voice in her head, telling her to set fire and kill herself. She says that her dead brother talked to her, and he was the one who set the fire that almost killed her and runs out, sobbing.
When he hears what Sam’s problem is, Castiel says that he can also heal spiritual illnesses. He is also able to sense that Dean is angry at someone who he believes betrayed him, and that Dean has killed a lot of persons. Looking suspiciously at Castiel, Dean says that the person he thought was responsible for Sam’s condition was dead. When he finally mentions the name “Castiel,” Castiel doesn’t react other then to say that it’s an unusual name.
The next morning, Dean stops at a convenience store to call the hospital. He goes inside and has Castiel wait in the car. The owner, possessed by a demon, attacks Dean. Dean manages to kill it but realizes that his phone was broken in the struggle. Two more demons attack Dean and get the upper hand, but someone kills them from behind. Dean assumes that it’s Castiel at first, but realizes that it’s the demon Meg Masters.
Meg admits that she isn’t on good terms with Crowley and has heard rumors about the healer. She’s seen him outside and is surprised that he’s actually Castiel. Meg suggests that they ally together now that the demons are after both of them, but Dean figures that she wants to use Castiel as a weapon. Meg doesn’t deny it but says that they have no one else to turn to and Dean has no choice but to agree. As they go outside, Castiel recognizes Meg as a demon but she assures him that she’s a friend of sort. When she starts hinting that she and Castiel have met before, Dean quickly gets them both into the car.
Sam approaches Marin again and apologizes for questioning her earlier. He assures her that he believes she didn’t start it and offers to help her deal. Marin explains that her brother died a year and then he started talking inside of her head. No one else could hear him, and at first Marin was happy to have her brother back. However, her brother started getting mad and yelling at her, and finally kept demanding that she join him. Sam asks Marin to trust him and says that he can banish the demon, and asks what happened to the body. Marin confirms that her brother was cremated, but that she has a cord bracelet with some of his blood on it. Satisfied, Sam asks if she can get a lighter.
Dean and Meg drive in silence and Castiel wonders if there’s something he should know about, but they insist that they don’t.
Marin steals a lighter from Marcus and brings it to Sam’s room. He tries to make a salt circle but Lucifer blows on it so Sam tells Marin to do it. Once she closes the circle, she and Sam get into it. Her brother’s ghost appears and begs her to stop, but Sam burns the bracelet and the spirit disappears. He gets Marin out of the room just as the orderlies come in and sedate him. Kadinsky examines Sam and considers a surgical solution.
When Dean, Castiel, and Meg arrive at the hospital, they discover that a small group of demons have tracked Sam down and are in the parking lot. Meg hints that they should let Castiel use his powers and Dean drags her off to the side. He warns her that they don’t know what Castiel will do if he regains his memories. When Castiel overhears them and comes over, Meg tells him that he’s an angel, and Castiel wonders why Dean didn’t tell him immediately. Dean warns that angels are bloody and corrupt, but Castiel has no memory of him or what he did. Meg tells Castiel to smite the demons and the angel agrees even though he’s not sure how to start. He goes into the parking lot and grabs one demon’s head. Golden light pours from its eyes, burning out the demon within. Castiel quickly kills the other demons and then turns to Dean as he arrives and says that he remembers everything... including the fact that he’s responsible for Sam’s current condition.
Marcus straps Sam to a gurney and takes him to an electroshock theater. However, he reveals that he’s demon-possessed and puts the headpiece on Sam.
Castiel insists that there was no defense for what he did, even though Dean assures him that he did the best he could. Unconvinced, Castiel thinks that he should have died, and wonders why he walked into the river to die if he couldn’t fix thing. Dean suggests that maybe he came back so he could fix things, and then goes to the car and hands Castiel his old coat back.
Marcus continues turning up the power, torturing Sam, but Castiel arrives and kills him. He apologizes to Sam and tries to heal him, but Sam sees him as Lucifer and Castiel realizes that he’s failed.
Later, Dean and Castiel come to visit Sam, who has lost all touch with reality. Castiel explains that he was too late and that Sam’s mind has crumbled entirely, leaving him nothing to fix. However, he realizes that he can transfer the damage. Before Dean can stop him, Castiel touches Sam’s head, says he’s sorry for what he did to him, and transfers his insanity into himself. Sam is restored to normal but Castiel is overcome by insanity and fear and backs up, horrified.
Sometime afterward, Sam and Dean leave the hospital. Sam is uncomfortable with what they’re doing, working with Meg, but Dean warns that all of their friends and allies are dead. Inside, Meg uses her charms to get Kadinsky to take her on as his newest doctor.