West Nile virus has emerged globally as a significant cause of viral encephalitis in humans. Infection of humans is associated with a febrile illness that can progress to meningitis and encephalitis with symptoms including cognitive dysfunction and flaccid paralysis. Following its introduction to the United States in 1999, West Nile virus rapidly disseminated across North America. Outbreaks of West Nile virus fever and neuroinvasive disease now occur annually in the United States, with about 23,000 diagnosed human cases between 1999 and 2006. The emergence of West Nile virus in the Western hemisphere and the corresponding increase in disease burden has been accompanied by intensive study. West Nile Encephalitis Virus Infection: Viral Pathogenesis and the Host Immune Response focuses on recent studies that have identified key steps in the molecular pathogenesis of West Nile virus infection. Chapters describe our most up-to-date understanding of the pathogenesis steps in animals and the viral sequence determinants mediating virulence, the earliest innate host immune response that controls West Nile virus spread, and novel approaches and prospects for human vaccines and therapeutics.