The season opener finds Michael Scofield in Sona, a hellish and deadly Panamanian prison where a previous riot has forced all authority out and has left the prisoners in charge of their own lives (and deaths). With the fate of his loved ones hanging in the balance, Michael must to find Whistler, a mysterious fellow inmate hiding within the prison's sewer system, in order to break him out from a prison from which there is no way out. Meanwhile, Lincoln searches for a missing Sara and receives troubling news about LJ on "Orientacion."

Michael races to find a hidden Whistler before Mahone; searching for clues outside the prison, Lincoln runs into an old friend and makes a new one; T-Bag slithers his way into Lechero's graces as the prisoners threaten a revolt due to the lack of agua (water).