It is the morning after their escape from Fox River, and the inmates narrowly avoid being caught by Bellick as they jump onto a freight train. FBI Special Agent Alex Mahone has been assigned to their case and calls a press conference urging the public to turn in the "Fox River 8." Michael, Lincoln, Abruzzi, C-Note, and Sucre encounter a hunter and his daughter. He holds them at gunpoint until Abruzzi grabs the daughter and forces the hunter to give them his SUV and let them go. The escapees head for a location where Michael has things stored. Agent Mahone tracks Michael's credit card to a storage facility in Oswego, but quickly figures out that one of Michael's tattoos holds the real location. Michael's tattoo "Ripe Chance Woods" is a clue pointing to a cemetery where Michael has items buried in the grave of "E. Chance Woods." Just two steps behind, Agent Mahone arrives at the scene just as the inmates have gathered what they need. In the meantime, T-Bag discovers a veterinary clinic and forces the Vet to re-attach his severed hand. Dr. Sarah Tancredi recovers from her overdose. Inside her purse, she finds an origami swan left for her by Michael with a message, "There's a plan to make all of this right", and a code. The code is a series of numbers which reads 3221243324 for the first line, 4221312231 for the second, and 23133121 for the third. Veronica locates Terrance Steadman in Montana, and finds that the doors are locked from the outside, holding him hostage (albeit willingly). Veronica calls 911, and then talks to Lincoln and tells him what she has learned. Employees of The Company arrive and kill Veronica for having unraveled their plot and for having found Steadman. Lincoln hears Veronica's final words as she dies, and is consumed with grief. Mahone studies Michael's tattoos, and feels that they are the key to finding the escapees.

Michael's plan has hit a snag when the home owner's daughter, a cop, arrives. Mahone argues with Lyle Sands about how to proceed, but ultimately hopes that Tweener, in FBI custody, will reveal the location of the other escapees. Sara is now suspicious of Kellerman, so he tries something different to find Lincoln Burrows. In an Arizona detention facility, L.J. finds out he's to be released the next day; Linc drives to get him. Haywire, in Wisconsin, steals supplies from a camping shop.

In his efforts to try to get hold of all of the money Sucre runs into some unexpected difficulties. And Captain Bellick and his partner have not given up on finding their old inmates.

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.

Michael is once again imprisoned, but now in SONA (Panama), together with T-Bag, Mahone and Bellick. The prison is solely ruled by inmates, whose local prison-lord Lechero feels threatened by Scofield's 'fame'. Lincoln tries legal means to get Michael transferred, and gets a call from a relative. Both receive the same message, through different channels, from The Company.

Lincoln tells Michael that they have four more days to rescue Whistler, but Michael is upset with his brother that he used him. Gretchen has a meeting with General and they decide to use power to release Whistler in an operation called "Bang and Burn". Later she asks Whistler to kill Michael. In Sona, the guards reinforce the bars in the windows, and Michael tells Lechero that this way it will be difficult to break-out. Sammy requests more men to Lechero to keep Sona under control. Sofia receives a call from Whistler's mysterious landlord telling that he has some "insurance papers" from her boyfriend, however, the Company intercepts the conversation. When Sofia receives the documents, she finds a passport of Whistler in the name of Gary Miller. But Gretchen arrives and takes the documents. Mahone tells Agent Lang how he killed Shales and then high from the pills, asks her to get some drugs for him otherwise he will not be able to speak in the hearing. T-Bag gives a message from Lechero with the blueprint of his cell with a hidden door and an access code. Whistler is ready to stab Michael when Lechero arrives and he hides the knife. Michael asks McGrady to request his father to call Lincoln and give him a message: "Don't come home for dinner." Mahone fails in the hearing and is sent back to Sona. Lincoln, Sucre and Sofia are attacked by the Company's agents and the brothers realize that something is happening, i.e., the Company does not need them anymore. When the "Bang and Burn" Operation begins, Michael catches Whistler and Gretchen fails in her intent. General Zavala has Michael hauled in for questioning over the attempted breakout.