This article reviews the history of smallpox and ethical issues that arise with its threat as a biological weapon.1 Smallpox killed more people than any infectious disease in history-and perhaps three times more people in the 20th Century than were killed by all the wars of that period. Following a WHO-sponsored global vaccination campaign, smallpox was officially declared eradicated in 1980. It has since been revealed that the Soviet Union, until its fall in the early 1990s, manufactured tens of tons of smallpox for military purposes. A worry is that some of this may have fallen into the hands of "rogue" nations or terrorists. Current U.S. debate questions whether smallpox vaccine should therefore be made available to the American public, which-like the rest of the world-now lacks immunity. Because the vaccine is considerably dangerous, public dialogue cannot resolve this matter if evidence material to the likelihood of attack is classified (i.e. secret). I conclude by recommending numerous future areas for ethics research related to the weaponization of smallpox.