World War II marked a watershed in the history of vaccine development as the military, in collaboration with academia and industry, achieved unprecedented levels of innovation in response to war-enhanced disease threats such as influenza and pneumococcal pneumonia. In the 1940s alone, wartime programs contributed to the development of new or significantly improved vaccines for 10 of the 28 vaccine-preventable diseases identified in the 20th century. This article examines the historical significance of military organizations and national security concerns for vaccine development in the United States.