In spite of its eradication in 1980, the threat posed by the use of smallpox as an instrument of terror has increased its salience to policy makers. Events of the 1990s and beyond have demonstrated the willingness and ability of terrorists to utilize biological weapons against Americans. Biological terrorism is unique in that it connects public health concerns with national security. As such, policy making on biological terrorism issues has tended to be housed in the executive branch bureaucracy (in particular the National Institutes of Health, Department of Health and Human Services, Department of Defense, and Centers for Disease Control and Prevention) until the threat environment causes a shift of the policy-making process into the White House. We contend that this phenomenon for smallpox policy occurred in both the William J. Clinton and George W. Bush administrations.