The COVID-19 pandemic highlights a long-known but often neglected aspect of international relations: the ability of disease to challenge and change all aspects of security, as well as the ability of public policies to change the course of disease progression. Diseases, especially mass epidemics like COVID-19, clearly affect political, economic, and social structures, but they can also be ameliorated or exacerbated by political policies, including public health policies. The threat of pandemic disease poses a widespread and increasing threat to international stability. Indeed, the political implications of pandemic disease have become increasingly evident as COVID-19 has precipitated death, economic collapse, and political instability around the globe. Any pandemic disease can precipitate catastrophes, from increasing health care costs to decreased productivity. This theoretical discussion highlights the intertwined interactions between social, political, and economic forces and the emergence and evolution of pandemic disease, with widespread implications for governance and international security.