One of the most devastating shocks to global security imaginable is a pandemic. As history helps to demonstrate, this catastrophe and its reverberations could in today’s world create a scene not unlike that depicted in the Book of Revelation, when the pale horse and its rider Death sow destruction “with sword and with famine and with pestilence.” To protect our own interests and security, it is imperative that the United States take preventive actions against a potential pandemic. This article argues that one important area for mitigation is climate change interacting with the growing urbanization of the world’s population. These two factors combined promise massive shocks to global security, and because of the destructive potential, it is critical that U.S. national-security professionals consider this worst-case future when developing policies and strategies. If a large-scale pandemic does occur, as many scientists believe possible, are we prepared to handle it? Have we taken the actions necessary to mitigate the worst-case outcome? This article also argues that a lead actor in prevention efforts should be the U.S. military, which has the reach and resources that others do not.