In the past thirty or forty years scientists, historians, and others have written many histories of the wonder drug, penicillin. However, almost all of these works fail to develop an important part of the history of penicillin: the attempt to synthesize the drug during the Second World War. Therefore, the purpose of this paper is to explore this largely unexamined episode in the history of science, and to answer some relevant questions. For example, why was there a need for synthetic penicillin? What organizational plans had to be made in order to accommodate this massive endeavor? What was the effect of the search for a synthesis on the natural production of this drug? And finally, did chemists ever devise a successful synthesis? Before attempting to answer these and other questions, a brief introduction to 1) the discovery and development of penicillin as a therapeutic agent, and 2) the general organization of wartime medical research in the United States and Great Britain, is necessary.