In Blue Earth, Minnesota, Pastor Jim Murphy is in his church when a wind springs up out of nowhere, and Meg Masters enters the church, She says she needs to talk to someone and says she's done bad things, and asks if there is forgiveness for everyone. Pastor Jim assures her that there is, and Meg tells him that she's lied, stolen, lusted, and slit an innocent man's throat. She reveals her demon eyes and Pastor Jim he says that she can't be on hallowed ground. When she says it only works on minor demons, Pastor Jim runs into the back and goes to a room filled with dozens of weapons. Meg kicks her way in and Pastor Jim throws a rune-inscribed knife at her. She catches it and says that she wants the Winchesters, and Pastor Jim says he hasn't spoken to John in over a year, and he wouldn't tell her if he did know where they were. Meg agrees, cuts his throat, and walks away.
In Manning, Colorado, John is showing his sons all of the newspaper clippings, weather reports, and research that he's done to track down the demon that killed Mary Winchester. He explains that he picked up its trail a year ago and took off, a trail that spread across the country. In each case, a house burned down and a six-month-old was taken, just like Sam was when Mary died. Sam continues to blame himself, and Dean argues with him until John breaks up the fight. He admits he's always been one step behind, but he's learned to trace the signs. The same signs occurred in Lawrence a week before Mary died, and in Palo Alto before Jessica died. The signs are starting again, in Salvation, Iowa.
The Winchesters arrive in Salvation and John gets a call from a friend named Caleb, who informs him that Pastor Jim is murdered. There were traces of sulphur there, and they wonder if the demon knows they're getting closer. John tells them to check for every six-month-old born in the area, and they'll keep an eye on all of them. As Dean leaves, he asks John if he's okay. John admits that he and Pastor Jim were close, and vows to end it no matter what it takes.
The Winchesters split up to check birth records. Dean meets an attractive receptionist and flirts with her. As Sam does the legwork, he gets a vision of a woman putting her baby daughter in bed, and a train going nearby. He checks the addresses he has against a map of the town and tries to get a fix on the house. A sudden storm springs up and Sam gets more visions of the woman in the nursery, confronting a man in a long coat. He spots the house and recognizes the window, and sees the woman walking her baby, Rosie. Sam claims to be a new neighbor and introduces herself to the woman, Monica Holt. Monica notes that Rosie never cries and seems to be able to read minds. Sam confirms that Rosie is exactly six months old, and tells her to take care of herself. Monica's husband, Charlie, pulls up, and Sam gets a vision of the nursery bursting into flames. He then sees the intruder telekinetically pinning Monica to the ceiling of the nursery and setting her on fire as her daughter looks on.
Back at the motel, Sam tells John and Dean what he saw. John blames Dean for not notifying him about Sam's visions, but Dean angrily notes that John has refused to take their calls and his father apologizes. When Sam says that the Holts will go through the same hell they went through, John says that no one ever will again. Sam gets a call from Meg, asking to speak to John. he tries to lie without success, and John takes the phone. Meg tells him that she killed Pastor Jim, and now she's in Lincoln and has Caleb prisoner. John tells her to let Caleb go, but Meg demands the Colt. When he denies having it, she cuts Caleb's throat and lets John listen to his friend dying. She repeats her demand and promises that she'll kill every friend he's ever had until he turns over the Colt. John agrees to bring her the Colt, and Meg directs her to a warehouse in Lincoln.
Afterward, John says that Meg is either a demon or possessed by one, and he's going to Lincoln. When Sam says that they need the Colt to deal with the demon when he comes after the Holt, John explains that he's going to give her a fake Colt to buy her a few hours for Dean and Sam to kill the demon. He admits he doesn't want to do it, but he wants it all to be over. Later, Dean gets a similar Colt from an antique shop and meets with Sam and John, John insists he can handle Meg, but Dean asks him to promise to get out if the situation is critical. John explains that there are only four bullets left, and the Colt is useless without them. He tells them that it's their fight now and to finish what he started, and then gives the Colt to Dean. Sam says that they'll see him soon, and John just smiles and says he'll see them later.
John drives to the warehouse in Lincoln and sneaks inside.
Sam and Dean watch the Holts and try to figure a way to get them out of the house. Dean figures all they can do is wait until the demon shows up and hit it before it kills the Holts.
John watches from the roof as Meg arrives. He then climbs up to the water tower, says a blessing over a cross, and drops it into the water inside.
As they wait, Sam thanks Dean for everything just in case, for being able to count on him no matter what. Dean tells him that nobody is dying and he doesn't want to hear any "just in case" speeches, and the only thing that will die tonight is the demon.
John confronts Meg, who demands the gun. He asks how he'll get out, and she says he'll figure something out. Meg calls in her assistant demon to back her up and then demands the gun. John hands it over, and she has her assistant examine it. He takes it and shoots Meg, but she doesn't die, revealing that it's a fake. John claims that he didn't know it was a fake, but Meg prepares to kill him. He runs into the steam tunnels beneath the warehouse, and Meg and her assistant pursue him. As they come at him, John opens up a vent. Meg sends her assistant into the water, and his feet start to sizzle. As they back up, John smiles and leaves.
Dean tries to call John but doesn't get an answer. The car radio starts to malfunction and a wind picks up, and they realize the demon is there.
John runs out to his truck, only to discover that Meg slashed the tires in advance.
Sam and Dean break into the Holt house. Charlie attacks them and Dean tries to tell him they're there to help, but he calls to Monica to get Rosie. Dean knocks him out, while Monica goes to the nursery and finds the demon standing over Rosie's crib. The demon pins her to the ceiling as Sam runs in. It glares at him with yellow eyes, and Sam tries to shoot it. The demon fades away before the bullet can hit. Sam and Dean get Monica and Rosie out just as the room bursts into flames.
As John tries to call his sons, the second demon arrives and telekinetically pins him to a wall.
Outside, Monica explains to her husband that Dean and Sam saved her and Rosie. Sam looks up and sees the demon in the nursery, and prepares to go in after him. Dean stops him, warning that it's suicide.
Later, Sam and Dean are at the motel and try to reach John on his cell phone without success. Sam blames Dean, saying that he should have let Sam go after the demon. He insists that he would have sacrificed himself to get the demon, but Dean refuses to let Sam sacrifice himself. He warns that sacrificing himself won't bring back Mary or Jessica. Sam grabs him, but Dean insists that John and Sam are all that he has. Finally, Sam gets hold of himself and tells Dean to call John again. In the warehouse, Meg picks up the phone and tells Dean that they really screwed up, and they're never going to see their father again.