Raymond "Red" Reddington, one of the FBI's most wanted fugitives, surrenders in person at FBI Headquarters in Washington, D.C. He claims that he and the FBI have the same interests: bringing down dangerous criminals and terrorists. In the last two decades, he's made a list of criminals and terrorists that matter the most but the FBI cannot find because it does not know they exist. Reddington calls this "The Blacklist". Reddington will co-operate, but insists that he will speak only to Elizabeth Keen, a rookie FBI profiler.

Steve McGarrett returns home to Oahu, in order to find his father's killer. The governor offers him the chance to run his own task force (Five-0). Steve's team is joined by Chin Ho Kelly, Danny "Danno" Williams, and Kono Kalakaua.