In the summer of 1999, West Nile virus (WNV), a mosquito-borne flavivirus native to Africa, Asia and Europe, was discovered in the western hemisphere for the first time when it caused an epidemic of human encephalitis in New York City and the death of thousands of birds in northern New Jersey and southeastern Connecticut. The virus successfully over wintered and spread rapidly throughout the region culminating in 2003 with over 300 human cases. Although the virus continues to persist, notable declines in activity were observed for the first time in 2004. WNV has been isolated from in 18 mosquito species in the region, but five species: Culex pipiens, Culex salinarius, Culex restuans, Culiseta melanura and Aedes vexans have been implicated as the most likely vectors. Our current understanding of the ecology and epidemiology of this exotic virus, its reservoir hosts and mosquito vectors in the northeastern US are presented.