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Michael gets medical attention from the most unlikely of places, and Charles Westmoreland returns to help uncover the true meaning of Scylla. Meanwhile, Lincoln and Sucre race to stop Gretchen before Scylla is lost forever.
Michael and Lincoln race to get Scylla back from Gretchen and her new partner who are just as determined to get a missing piece of the puzzle from the brothers. Meanwhile, Mahone meets with an old colleague who is torn between friendship and duty, and T-Bag's faith is put to the test while holding Gretchen's family hostage.
Lincoln and his new partners arrive in Miami to recover Scylla from its shocking new owner, and Sara searches for a missing Michael who learns some surprising info about his past. Meanwhile, a double-crossing leads to a death and an arrest.
The major storyline for the fourth season is about a team recruited by Homeland Security agent Don Self to obtain the Scylla. Although the team initially believes it to be The Company's "black book," it is later revealed to contain information on an advanced renewable power cell.