The program traces the development of game theory with particular reference to the work of John Nash (famous from "Beautiful Mind"), who believed that all humans were inherently suspicious and selfish creatures that strategized constantly. Using this as his first premise, Nash constructed logically consistent and mathematically verifiable models, for which he won the Nobel Prize in Economics. He invented system games reflecting his beliefs about human behavior, including one called "So Long Sucker---F*ck Your Buddy", in which the only way to win was to betray your playing partner, and it is from this game that the episode's title is taken. These games were internally coherent and worked correctly as long as the players obeyed the ground rules that they should behave selfishly and try to outwit their opponents, but when RAND's analysts tried the games on their own secretaries, they instead chose not to betray each other, but to cooperate every time. This did not, in the eyes of the analysts, discredit the models, but instead proved that the secretaries were unfit subjects.

What was not known at the time was that Nash was suffering from paranoid schizophrenia, and, as a result, was deeply suspicious of everyone around him—including his colleagues—and was convinced that many were involved in conspiracies against him. It was this mistaken belief that led to his view of people as a whole that formed the basis for his theories. Footage of an older and wiser Nash was shown in which he acknowledges that his paranoid views of other people at the time were false.

Curtis examines how game theory was used to create the USA's nuclear strategy during the Cold War. Because no nuclear war occurred, it was believed that game theory had been correct in dictating the creation and maintenance of a massive American nuclear arsenal—because the Soviet Union had not attacked America with its nuclear weapons, the supposed deterrent must have worked and the theories would later be propagated through other segments of society.