The first identifiable case of West Nile virus (WNV) appeared in Uganda in 1937. Since then, WNV has been recorded in all six inhabited continents. In 1999, the first case in North America appeared in New York State; this heralded a new, more virulent chapter in the natural history of this virus. The spread of this arthropod-borne disease occurs primarily through the bite of the blood-feeding mosquitoes, although transmission has been shown to occur (rarely) by several other routes (faecal-oral, carnivory and blood-borne). In North America, WNV has demonstrated the ability to infect a broad host range of birds, reptiles and mammals, including humans. Increases in mosquito populations can serve as useful indicators of increased WNV activity. Therefore, controlling mosquito populations (larvicide and adulticide) is useful in reducing the risk for WNV infection. For prevention in animals, two vaccines are currently approved in the United States (no information on approval in other countries was collected) but have not been validated across a broad array of species. More research must be carried out to characterize the effects of the uses and misuses of the vaccines and other WNV control and prevention methods. Perhaps most telling in the case of this ‘new’ WNV (as with the introduction of many emerging diseases) in North America is the amount of information we still do not have on its ecology and natural history. As such, this chapter is not an attempt to provide an integrated worldwide view of this issue to readers in all parts of the globe; it is an attempt to summarize, or provide reference to, the important points of the North American experience to zoological managers around the world so that each will know the basics and integrate this information into her/his own particular risk-management scenario.