West Nile (WN) virus is a mosquito-borne flavivirus and human, equine, and avian neuropathogen. The virus is indigenous to Africa, Asia, Europe, and Australia, and has recently caused large epidemics in Romania, Russia, and Israel. Birds are the natural reservoir (amplifying) hosts, and WN virus is maintained in nature in a mosquito-bird-mosquito transmission cycle primarily involving Culex sp mosquitoes. WN virus was recently introduced to North America, where it was first detected in 1999 during an epidemic of meningoencephalitis in New York City. During 1999–2002, the virus extended its range throughout much of the eastern parts of the USA, and its range within the western hemisphere is expected to continue to expand. During 1999–2001, 142 cases of neuroinvasive WN viral disease of the central nervous system (including 18 fatalities), and seven cases of uncomplicated WN fever were reported in the USA. Most human WN viral infections are subclinical but clinical infections can range in severity from uncomplicated WN fever to fatal meningoencephalitis; the incidence of severe neuroinvasive disease and death increase with age. Serology remains the mainstay of laboratory diagnosis. No WN virus-specific treatment or vaccine is available. Prevention depends on organised, sustained vector mosquito control, and public education.