Prison Break follows the story of Michael Scofield, a structural engineer who gets himself incarcerated in Fox River State Penitentiary to break out his brother Lincoln Burrows, who's on death row for a crime he didn't commit. With the help of his cellmate Fernando Sucre and other inmates, Michael sets out to prove Lincoln's innocence and free him from prison before it's too late. But as their plan unfolds, they face unexpected challenges and dangerous obstacles that put their lives at risk. Will they be able to pull off the ultimate prison break?

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Sommige tv-series met vergelijkbare genres en die rond dezelfde tijd als Prison Break zijn geproduceerd, omvatten Vikings, Warrior, 9-1-1: Lone Star, Person of Interest, NCIS, S.W.A.T..