West Nile Virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, yellow fever virus, and Dengue virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. It has rapidly spread across the United States with cases being observed in every continental state. Virus particles consist of a dense core made up of the core/capsid protein encapsulating the RNA genome surrounded by a membrane envelope embedded with envelope and matrix proteins. While the viral core protein is thought to contribute to the WNV-associated inflammation via apoptosis induced though the caspase-9 pathway, the highly glycosylated envelope protein plays a major role for WNV entry into target cells as this entry can be inhibited by using a recombinant domain III from the envelope glycoprotein. The WNV receptor has recently been identified as alpha v beta 3 integrin.