West Nile virus (WNV) (Flavivirus: Flaviviridae) is the most widespread arbovirus in the world. A significant range expansion occurred beginning in 1999 when the virus was introduced into New York City. This review highlights recent research into WNV epizootiology and epidemiology, including recent advances in understanding of the host-virus interaction at the molecular, organismal, and ecological levels. Vector control strategies, vaccines, and antivirals, which now must be considered on a global scale, are also discussed.