West Nile (WN) virus is a mosquito-borne flavivirus that is native to Africa, Europe, and Western Asia. It mainly circulates among birds, but can infect many species of mammals, as well as amphibians and reptiles. Epidemics can occur in rural as well as urban areas. Transmission of WN virus, sometimes involving significant mortality in humans and horses, has been documented at erratic intervals in many countries, but never in the New World until it appeared in New York City in 1999. During the next four summers it spread with incredible speed to large portions of 46 US states, and to Canada, Mexico, Central America and the Caribbean. In many respects, WN virus is an outstanding example of a zoonotic pathogen that has leaped geographical barriers and can cause severe disease in human and equine. In Europe, in the past two decades there have been a number of significant outbreaks in several countries. However, very little is known of the ecology and natural history of WN virus transmission in Europe and most WN outbreaks in humans and animals remain unpredictable and difficult to control.