The first serious external threat to the mafia's existence in America comes from U.S. Attorney General Robert F. Kennedy, who repeatedly expresses his desire to eradicate organized crime in America. Kennedy unleashes the full force of the U.S. Justice Department, including a slumbering FBI that Kennedy will drag into the fray, to the apparent dismay of long-time FBI Director J. Edgar Hoover. The mafia's unforgiving response is executed by Louisiana don Carlos Marcello along with Florida don Santo Trafficante, who together take aim at the attorney general's brother, the president of the United States.

With the president dead and the attorney general out of office, things return to normal for the mob--but internal problems begin to appear within a number of borgatas, shaking the mafia to its core. Mobster Joe Valachi becomes the first-ever public informant when he testifies before a senate sub-committee, while Brooklyn mobsters Larry, Albert, and Crazy Joe Gallo launch an insurrection against the founder and leader of their borgata, Joe Profaci. While the Gallo-Profaci civil war is winding down, don Joe Bonanno challenges the mafia's ruling body, the Commission, in a situation that decides if the Commission's central authority can overpower the autonomy of each individual boss.

As he did in the first volume of this epic history, Louis Ferrante continues to debunk myths while adding new insights into other mafia mysteries, such as the feud between mafia capo Anthony "Tony Pro" Provenzano and union leader Jimmy Hoffa, revealing the most plausible scenario of why Hoffa died, how he was killed, and what happened to his body.