The article first explores the history of smallpox, showing how the disease has ravaged populations and how the world achieved a collective victory over the disease through industry, collegiality, and resourcefulness. Still, there is concern that the world's collective guard has been eroded, exposing the world once again to this disease. The decisions remaining are whether to destroy the virus, conduct additional experiments upon it, or retain it indefinitely. The second part of the article examines the security dimension of the issue, noting how smallpox has been one of the few biological agents that has been regularly considered, occasionally developed and stockpiled, and episodically used as a tool of warfare and terrorism. The third section of the article presents a lay person's introduction to genetic engineering, especially the ways in which the most sophisticated DNA manipulations now open the door for reformation of the genetic legacy of creatures, from bacteria to sheep to human beings. There is a danger that the viral genome may be manipulated in similar fashion to render variola even more deadly and impervious to human defenses. Even worse is the possibility that it may already have happened, as defectors from the Soviet enterprise claim. The fourth part of the article summarizes how the world has thus far responded to the aforementioned potential threats. It reviews the misguided efforts of the World Health Organization, the American and Russian resistance to destroying the last variola samples, and the spasmodic reaction to the terrorist attacks of September and October 2001, including the procurement of vast quantities of an old, highly successful, but still problematic anti-smallpox vaccine. The article concludes with recommendations for a revised future course. Various legal instruments are reviewed, including treaty amendment, codification of public health statutes, upgrading national and international scientific research facilities, and enhancement of international cooperation. The article advises that the world must draw upon all its resources to avoid the horrors of smallpox biological terrorism. 541 footnotes