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.

Now that Caroline Reynolds has stepped down as president, she can no longer sign a pardon, so the brothers must immediately disappear, forever. At the pier Sarah realizes she's being tailed and pretends on the phone already to be on board, so they sail without her while she is arrested. Lincoln stops Michael from returning for her. A week later, an FBI bigwig offers C-note a lesser sentence for testimony against Mahone, even freedom and witness protection for his family- bingo. Fernando grabs Bellick's gun while looking for T-bag, but Bellick shows a crucifix to prove he has Maricruz. The scumbag enjoys his fortune with a lady of the street playing his Susan-Q. The brothers arrive at Cristobal, Panama. Meanwhile Malone's team deduces Scofield's tattoos refer to Michael's mother Christina, presumably dead, and he presumes his computer contained much info on Panama for a reason. The man in power grills Kim on a small boat, and decides to change the strategy. Mahone sees through FBI-colleague Wheeler. C-note is reunited with his family and released. The brothers have a fight, torn by guilt for too many innocent people suffering through their well-meaning deeds, then board a yacht, named- Christina. Mahone tells Kim he's not happy with the results as he remains separated from his family, but is told he now needs help to escape, and therefore must go to Mexico- to help T-bag.

Tyge tells Michael that he and Whistler were co-employees at the McFadden, a hotel in Nice, France. Mahone worries about Tyge's constant, keen observance of Whistler. Having to re-plan hastily, Michael tells Linc to find out the location of the nearby cafe and drug the guard's coffee, and also demands pictures of LJ and Sara before he escapes. Tyge is stabbed to death. Lechero questions McGrady and has Whistler dragged away for a confession. Michael believes Mahone and Bellick's denials. T-Bag offers Michael a ring he stole from Sammy (his rival for Lechero's confidence), to use to frame Sammy for Tyge's stabbing. Michael finds the murder knife under Mahone's bed and goes to Lechero to denounce Mahone, only to find he has just walked out of the prison. Agents Richard Sullins and Felicia Lang arrive at Sona to present Mahone with a plea bargain from the US Justice: a term reduction to 8 years for testimony against the government conspiracy and Lincoln. He could be out in 4 years, but Mahone refuses, now he faces life imprisonment. Lechero administers justice for Tyge his own way. Linc and Sofia succeed in drugging Captain Hurtado, but Susan finds out the brothers had a different timing planned and threatens LJ's life. With no recent pictures available, Linc confesses Sara's death, causing Michael to make a drastic decision.

Mahone is assured all he has to do is tell the truth, enjoying full immunity. Michael tells Whistler their row is part of a diversion, the escape is now or never, before the drug in the guard's coffee wears off. Just when the critical sun reflection blinds the other tower guard, they must wait and hide till Sammy has passed, but get through the cut bars. They climb down, but the glare disappears so they must climb back up as there is not enough time to escape. They get back in time and out to the courtyard, but Lechero refuses to allow them to cancel their duel to the death in the courtyard, which had been intended as a fake diversion. Sofia draws a gun on Lincoln to prevent him from turning Whistler over to killers. He retorts that's condemning an innocent L.J. to death. Guards wake the passed-out Captain Hurtado, see the climbing rope and storm into the prison. The Colonel shoots Papo, one of Lechero's crew, 'for not telling' and exposes his deal with Lechero, questioning if he's the right man for the job. Hearing the Sona siren, Linc flees by car and when Susan calls, he lies, telling her he has the 'escapees' in the trunk, but Pike, another company operative phones her: the roll-count was complete. Sucre stops her van by crashing into it, but even when Linc holds her at gun-point her accomplice won't trade L.J. He releases her and gets a short extension to find out what happened. Failing a hearing, Malone now believes Justice official Richard Sullins is setting him up to confess. Michael is dragged before Lechero, but not to be punished, he's ordered to take the fallen boss along when he and Whistler escape. Susan asks instructions from Whistler, he tells her - as Gretchen - to give the brothers four more days.

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.

Michael and Sara's newfound happiness is short-lived, as Sara soon finds herself in prison, and Michael must break her out before a vengeful Krantz has her killed.