This chapter reviews the experimental evidence for persistence of West Nile virus (WNV) in vertebrates. Results of studies in monkeys, hamsters, and birds all indicate that WNV can produce an asymptomatic persistent infection in immune competent vertebrates. In the case of hamsters, the most thoroughly studied model, the infected animals develop a persistent renal infection with chronic shedding of WNV in their urine. Similar reports with a diverse group of other flaviviruses suggest that persistent infection is not a rare phenomenon and that it may be a general characteristic of viruses in this genus.