Flashbacks provide exposition on how the inmates arrived at Fox River Penitentiary from The Company's framing of Lincoln to the creation of Michael's plan to save his brother's life.

Michael tries to retrieve an item from Blanding Botanical Garden in Utah, but Mahone's people got to it first. Mahone believes that someone on his team is leaking information to the press; meanwhile Michael does some research on Mahone at an Internet café, then makes a trip to Durango, Colorado, to see a woman there. Linc and L.J. are on the road in Arizona. C-Note is in Chicago, and Agent Lang tries to use his wife to capture him. Bellick and Geary phone C.O. Patterson, at Fox River, to get information on where they should look for T-Bag. Sara is at a motel in Elgin, Illinois, trying to crack Michael's code. T-Bag arrives in Tribune, Kansas, for (as he puts it) "romance". Kellerman is on the trail of Sara.

The Border Patrol arrests Michael and Lincoln, saving them from Mahone that claims that wants his life back. Sucre crosses the border and jumps in a parachute in the Sonora Desert in Mexico. T-Bag goes to a war veteran bar in Pratt, Kansas, and steals a prosthetic job from a veteran sergeant. Michael and Lincoln are apprehended in the Border Patrol Holding Facility, in Las Cruces, New Mexico, waiting for transportation to Fox River, but Bill Kim orders Mahone to kill them. T-Bag meets Denise, who works in the post office, and seduces her to get Susan Hollander's address. Bellick is sent to the District Court in Greeley County, Kansas, and has his bail denied. He makes a deal to be sent to Fox River expecting to have a good life. However the new warden decides to use him as an example of the new administration. Meanwhile Mahone tries to transport the prisoners, but the standard procedure does not allow it. Kellerman makes an arrangement to intercept the convoy in a blocked tunnel to kill the prisoners. However, Michael and Lincoln and helped by a surprising allied. T-Bag finds Susan.

Linc and Michael have decided to take the keys and escape, figuring at least they'll go down fighting. FBI Special Agent Alexander Mahone chased them while staying in contact with Secret Service Special Agent Paul Kellerman who suddenly shot Mahone and gave the brothers a ride because he wants revenge on the White House; Linc wants his instead, but is offered the location of Terence Steadman. T-bag visits his ex-girlfriend, who tells him the children think he's their Uncle Teddy on an oil rig, but he moves in; when she goes for a gun, he attacks her and her son attacks Zach him, so he turns the home into a private prison. In prison, former boss Bellick, who naively had made a deal in order to do his time in Illinois, shivers in general population among the prisoners he abused and their mates, he has none as the new warden sees him as an example of his new, clean ship; he soon realizes there's no pleasing them, and tries hitting hard; a loyal guard warns him the night shift is on his enemies side as he treated them badly. Benjamin Miles 'C-Note' Franklin tries to save his Kacee who is in custody, advising her to put all the blame on him; after hearing how scared his girl is, he asks one of his friends for help to run while she's on bail but the judge refuses bail. Mahone awakes in hospital, and reports to Kim on Kellerman's betrayal and the brothers' escape, which is hitting the TV news, but refuses to play anymore, even if that means jail; when his wife Pam phones their son is hurt he rushes out for Colorado, but is stopped to hear it's a warning to force him back in line; however he is through doing Kim's bidding and shoots his man. Kim calls Steadman's bodyguards: he must be evacuated to a safe house as Kellerman knows his residence, but he is already there with the brothers- Kims orders to kill everyone, but only the FBI men are shot; Kellerman explains Steadman is made unrecognizable, including plastic surgery, so their only option is to get him to Washington, where FBI agents who know can still make the truth stick. Michael decides instead to turn himself in while informing the press, despite Kellermans gun aimed at him, but Steadman prefers to commit suicide, and his corpse is worthless for the brothers.

Sara meets Michael and Lincoln in a train station in Evansville, Indiana; when she sees Kellerman with them, she becomes disturbed and upset. Kellerman tells that she has a key of a private cigar club in Chicago. Caroline calls Kellerman and he tells that he is heading to Chicago by train, and she promises his life back, inclusive the chief of staff position. T-Bag tells Susan that they are passing through an "adjustment period" in their lives; when she tells him that she will have a guest called Patty Wallace, T-Bag welcomes Patty with a magnificent family brunch and uses the strong father figure to discipline Zack, seducing the guest with his charm and attitude. Wheeler is reporting the actions of Mahone to the FBI Headquarter and they find that Haywire killed a man in Algoma, Wisconsin. Mahone visits Bellick in River Fox, releases him using a habeas-corpus to make his dirty work, and gives a car, a pistol and an FBI badge to the despicable man. Bellick chases and traps Haywire, and waits for Mahone. In Benson, Minnesota, C-Note and Dede are leaving a snack bar when an addicted thief announces a heist. When Kellerman sees a road block on the train, he realizes that he was betrayed.

Michael Scofield and Sara Tancredi fail to get the tape from the Corona de Oro cigar club in Chicago, where security was at the ready, and turn to former warden Henry Pope, a club member, but he wants to call the police. Michael draws his gun and hands it over to prove his veracity; Sarah convinces him to go in with her late father's humidor key and he finds a computer memory stick. In Mexico, Fernando Sucre has car trouble and gets a ride from an Ixtapa airport security employee who sees his wanted-poster just after they parted at the airport, so he must run with his bride. T-bag and his forced-along family find his own house vandalized and looted except for the family bible, which arouses in him youth memories of his perverted father, and assures Suzy he wants their love and is happy to be infertile, her bloodline should take the Bagwells's place. When she refuses, he locks them up, considers ax-murdering but just leaves them behind. FBI Special Agent Alexander Mahone has tracked down Benjamin Miles 'C-Note' Franklin and his daughter, but lets them escape in a bus rather than shoot the kid. C-Note brings her to a doctor, worried about the kidney disease PKD, but won't allow inserting a catheter, rather turns himself in to Mahone, who is with his own boy in Colorado, and makes a deal to get him Scofield. Pope is out of the club, but is greeted at the entrance by Secret Service Special Agent William 'Bill' Kim whom only Paul Kellerman, watching from a roof with Linc, knows by sight. Michael drives over Kim and gets away with Pope, Sarah and Linc, locking Kellerman out. When Michael tells the others he's prepared to honor his promise to Pope (which the others didn't know about) to turn himself in for his help, Henry hands him the stick and lets them go.