The poxviruses form a large family of complex DNA viruses that infect both vertebrate and invertebrate hosts. The most notorious member, variola virus, was responsible for smallpox, one of the most dreaded of all infectious diseases. In the late 18th century, Edward Jenner demonstrated that smallpox could be prevented by immunization with a more benign relative, vaccinia virus, which caused mild infections in cattle. Ultimately, global vaccination strategies led to the eradication of smallpox.