The worldwide eradication of smallpox, certified in 1980, is one of the greatest public health achievements in history. Smallpox was a highly contagious, painful, and disfiguring disease. The Fifty-second World Health Assembly, May 17-25, 1999, in Geneva, Switzerland, reaffirmed the decision of previous assemblies authorizing the temporary retention of remaining stocks of variola virus in 2 designated laboratories, one at the Centers for Disease Control and Prevention in Atlanta, Ga, and the other at the Institute for Viral Preparations in Novosibirsk, Russia. Virus was retained in these laboratories to develop a safer smallpox vaccine, should the disease reappear. The virus was then to be destroyed. The Pentagon has had a program to develop a new smallpox vaccine, but this vaccine will not be available until 2004. The present concern is that smallpox virus will be procured and used as a weapon of bioterrorism. On January 24, 2003, vaccination programs were begun using the old Dryvax vaccine that was used in the last century. This is a live virus vaccine. There are several complications of the Dryvax vaccine, including postvaccinal encephalitis (PE). The clinical presentation and treatment of this complication will be reviewed to prepare physicians, should they need to care for patients with this disease.