In 1999, an outbreak of human West Nile encephalitis occurred in New York City. During the outbreak, 62 cases of human West Nile virus (WNV) infection were diagnosed, with 7 deaths. This was the first time that human WNV infections were detected in the Western Hemisphere. By 2002, the total number of human cases of WNV that year alone reached 4156, with 284 fatalities. In addition, investigations have shown that WNV can be acquired through organ transplantation, blood transfusion, breast milk, transplacental transmission, and occupational exposure. This article provides an overview of the 2002 WNV epidemic in the United States and reviews the epidemiology of WNV, the clinical presentation of human WNV infection, and the prevention and control of this emerging pathogen.