The study of poxviruses has a long and distinguished history that includes Jenner’s founding work on smallpox vaccination. In the more than 200 years since that time we have seen the remarkable eradication of smallpox. It is difficult to overstate the significance of that achievement. It not only removed a disease that must rate as one of humankind’s greatest scourges, but also demonstrated the effectiveness of the general principle of vacci- tion in our battles against disease. This book begins with a review of smallpox and its causative agent, Variola virus. The vaccine used in the successful smallpox eradication c- paign, vaccinia virus, is reviewed in the following chapter that describes its origin and its use as a vaccine, as well as the current understanding of the molecular biology and pathogenesis of this virus. Vaccinia virus is the most intensively studied poxvirus and the descriptions of the biology of this virus are relevant to all vertebrate poxviruses. The eradication ofsmallpox has drawn attention to the potential threat posed by other orthopoxviruses that infect humans, particularly Monkeypox virus. A description of this virus is given in the third chapter. Jenner’s ori- nal vaccine is believed to have been Cowpox virus and this virus is reviewed in the chapter by Essbauer and Meyer. Additional chapters are devoted to each of the recognized genera of the vertebrate poxviruses and a f- ther chapter describes the subfamily of poxviruses infecting invertebrates. Together these provide a comprehensive review of the poxvirus family.