Sam and Ruby are interrogating a demon about Lilith's whereabouts but the demon is defiant. He taunts Sam until the latter forces the demon from the body with his psychic abilities. Ruby looks on with approval… and they're both unaware that Dean is watching them from the shadows. As he tries to reassure the human host, Sam assures Ruby that the headaches have gone. Dean comes in and demands to know what's going on. He realizes who Ruby is, in her new host body, and attacks her. Sam manages to separate them and Ruby takes the human host outside while Dean stalks off, angry.
Later, Dean returns to the hotel and starts packing to leave, then punches Sam repeatedly and wonders what Sam has been doing. Sam apologizes and explains that his way, most of the victims survive. Dean warns that it's a slippery slope and that if he didn't know Sam, he'd be hunting him. Sam explains that he had to find a way to fight when Dean was gone. Dean explains that Castiel wants it stopped, meaning God doesn't' want it involved. They're interrupted when Sam gets a call from a man named Travis about a man named Jack Montgomery in Carthage, Missouri.
Jack is on his third steak as his wife Michelle looks on in astonishment. Later he brushes his teeth and suffers from sudden intense pain. His back contorts and twists in agony.
Sam and Dean head for Carthage and Dean explains what happened to him in the past. He admits that their mom and dad were awesome, and Sam wonders what the point is of the Yellow-Eyed Demon bleeding in his mouth. Realizing he didn't describe that part of his encounter, Dean gets Sam to admit he knew about the demon blood for a year.
Jack goes down to get a snack, unaware that the Winchesters are watching him. He starts eating all the meat in the refrigerator, literally stuffing it into his mouth whether it's cooked or uncooked. They return to the hotel to find an old family friend and Hunter, Travis. He explains that Montgomery is a Rugaru, a flesh-eating monster that starts human and transforms into a demon that eventually seeks out human flesh. Once they get a bite of human flesh, they transform forever. Travis killed Jack's father, who passed on the condition to his son. Travis had hoped that Jack didn't have the affliction but has discovered otherwise.
At home, Michelle is preparing supper when she cuts her finger. Jack stares at her blood in fascination, but then runs out before he can give in to his new urges. He goes to a bar and starts eating all the peanuts, then notices a man hitting on a girl. Jack tells the man to get lost and insults him, then catches the man's fist when he throws a punch and breaks his hand. Jack runs off in horror at what he's done.
Dean and Travis prepare blowtorches to kill the Rugaru while Sam returns with the research he's been doing. Some Rugaru have never transformed as long as they avoid eating human flesh. Travis insists they're fairy tales and every Rugaru he knows has given in to its impulses. Sam suggests they explain what's going on to Jack so he can fight it, but Travis disagrees. Sam refuses to kill Jack unless he does something evil. He storms out and Travis wonders what the matter is.
Jack returns home and Michelle is angry at him for abandoning her. He apologizes and she eventually accepts it and he starts to make out. He becomes increasingly violent, biting at her neck, and she shoves him off. He runs out, upset.
As they drive to Jack's home, Dean wants to know if Sam is going to follow through if he needs to. Sam insists that they give Jack a chance and Dean wonders if Sam is too emotionally involved. Sam tells Dean to pull over and then explains that he's been lying to Dean because Dean has been treating him like a freak. He admits that he does feel like a freak because of the blood curse, and he's trying to make something good out of it. Dean agrees they should talk to Jack and they go to his house where Jack is out watering the lawn. They explain what's happening and Jack admits he's been noticing strange things going on. Dean explains what will happen and that they'll have to stop him, but Jack orders them off of his property.
Jack walks the streets and refuses to take Michelle's calls. When he sees a woman undressing in her bedroom window, he climbs up and Dean and Sam go after him. Jack sees himself in the window and leaves, while Sam and Dean burst into the woman's room and make a hasty exit. Jack returns home to greet Michelle, only to discover her tied up. Travis grabs him from behind and chloroforms him unconscious.
Jack wakes up tied up next to his wife. Travis apologizes and explains that Jack will eventually transform. He tells Jack to explain and Michelle demands an answer. Travis tells Michelle to reveal what she told him: that she's pregnant. Travis prepares to kill both of them and Jack goes into a frenzy, transforming as he thinks of his wife dying. He breaks free and attacks Travis, breaking his arm. Jack bites into Travis' neck and rips out a chunk of flesh, then feeds. Michelle looks on in horror as Jack turns to her, covered in blood. He advances on her… and unties her. She tells him to stay away and runs outside to her car. Jack advances on Travis' corpse while outside, Sam and Dean arrive. They enter the house and see the blood trail, and follow it to Travis' mostly-eaten corpse. Jack attacks the brothers and knocks them out.
Sam wakes up locked in a closet, Jack is outside and tells him Dean is alive and Sam needs to calm down. Jack thinks that Sam sent Travis there to burn his wife alive. However, when he realizes Sam doesn't know about Michelle's pregnancy, he doesn't mention it. Jack starts lapping up the unconscious Dean's blood and realizes he can never see his family again. As he talks to Jack, Sam uses a coat hanger to try and pick the lock and explains that he knows what it's like to have a monster inside. Jack tries to restrain himself but reaches for Dean… and Sam breaks out. He grabs the blowtorch and sets Jack on fire, killing him.
Later, Dean tells Sam that he did the right thing and there was no going back for Jack. He apologizes for being hard on Sam and admits the psychic thing scares him. Sam would rather not talk about it but Dean demands an explanation. Sam says he has to deal with it, and Dean assures him he doesn't have to do it alone. Sam says he's done with using his powers: he's choosing it for himself, not for Dean or God or anyone else.