As the industrial revolution spread throughout the Western world in the 19th century, nation-states institutionalized disease control. Formal institutionalization was only possible because in 1796 British physician Edward Jenner (1749-1823) created the first smallpox vaccine. Following this innovation, Western nations orchestrated campaigns and other organized efforts to limit the spread of smallpox. But couched within this guise of public health and human welfare, the vaccine enabled nation-states to establish greater state power and legitimacy in their home countries and colonies. This article argues that from the early 1800s until the 1980s, Western nations used Jenner's smallpox vaccine not only to improve human health, but as a tool to propagate their social and economic agendas. Tracing the smallpox vaccine within its historical context raises important questions about the role of physicians, medical innovation, public and global health, and health diplomacy.