As eight hours has passed since the escape, Michael, Lincoln, Sucre, C-Note and Abruzzi attempt to evade their seekers. Bellick is forced to relinquish the command of the search party to FBI Special Agent Alexander Mahone whose ingenious approach makes Michael's life as a fugitive harder. As a result from her overdose, Dr. Tancredi is in critical condition. A short-handed T-Bag faces the ultimate challenge.

Bellick gets a taste of the medicine he gave out when he was the Captain and Agent Mahone's ex-wife makes another appearance.

T-Bag digs deep and finds his 'nice-side' with the help of a psychiatrist. Michael, Lincoln, and Sarah get their hands on evidence needed to bring down The Company, while Kellerman is close to finding the President.

An unlikely alliance forms between Bellick and Sucre while Michael is determined to face the president. T-Bag gets into some trouble when he loses his luggage and C-Note faces major consequences after some of his actions.