This chapter discusses the history of drug use in Major League Baseball (MLB). It begins with Twentieth-Century Fox's baseball fantasy It Happens Every Spring, the story of a nerdy chemistry professor, and diehard baseball fanatic, who relies on a secret chemical formula in order to moonlight as a phenom pitcher for the St. Louis Cardinals. The problem with the film was that it was “the story of a cheat, winning a pennant and a World's Championship series.” In real-life baseball, cheating has quite a long history. This chapter examines the emergence of a generation of pioneering trainers and team doctors who introduced new methods to ease pain, spur healing, and enhance the performance of baseball players, including the injection of tranquilizers and the use of amphetamines. It also considers the case of Sandy Koufax and the league's refusal to admit that there was a doping problem in the sport; in short, baseball players did not use drugs.