Ex-government agent and one of the FBI's Most Wanted fugitives, Raymond "Red" Reddington (James Spader) mysteriously turns himself in to the FBI and offers to give up everyone he has ever worked with including a long-thought-dead terrorist but under one condition - he'll only talk to newly-minted female FBI profiler, Elizabeth Keen (Megan Boone) with whom he seemingly has no connection. For Liz, it's going to be one hell of a first day on the job and what follows is a twisting series of events as the race to stop a terrorist begins.
Po kemičnem napadu na washingtonski podzemni železnici je Red prepričan, da je na delu Frederick Barnes, bivši znanstvenik pri ameriškem obrambnem ministrstvu, ki že pet let kemično orožje prodaja najvišjim ponudnikom. Red namerava do Barnesa priti prek človeka, ki mu je prodal radioaktivni izotop, s katerim so se zastrupile žrtve na podzemni, Liz pa medtem odkrije, da ima Barnes redko bolezen, na katero bi s kemičnimi napadi rad opozoril oblasti in jih prisilil, da zanjo najdejo zdravilo.