The current evolution of West Nile Virus (WNV) disease with increase in the frequency, number and severity of cases in many countries reveal that new epidemiological scenarios are being appeared all across the world. The first United States (US) outbreak of WNV occurred in New York City in 1999; 68 human infections, mostly as encephalitis and meningitis were reported, resulting in 7 deaths. Since 1999, WNV epidemics have re-emerged again with about 30,000 confirmed human cases and more than 1,000 deaths through 2006. Analysis have revealed that spread of a new WNV dominant genotype, named WN02, which has been rising in the US since 2002. Phylogenetic comparison of complete and partial nucleotide sequences from US isolates found between the 1999 and 2000 outbreaks with WN- NY99 isolate revealed a high level of genetic similarity. The study of 22 WNV isolates from 2001-2002 revealed genetic diversity compared with WN-NY99 genotype. More than 70 viruses are included within the genus Flavivirus which have wide global range. Some geographically important flaviviruses which causes infection in humans include JEV, Zika virus (ZIKAV), Dengue virus (DENV), Murray valley encephalitis virus (MVEV), WNV and Yellow fever virus (YFV). Utmost number of these viruses is responsible for hemorrhagic disease, encephalitis clinical expression such as capillary leakage and fever finally leading to death. According to analysis, more than half of the world population suffering from the viral infection risk by WNV, DENV, ZIKAV, JEV and YFV. WNV transmission usually occurs by the bite of an infected Culex species mosquitoes to healthy human and horses. Culex species mosquitoes have been recognized as the most important vector for transmission of WNV infection. Humans either most commonly get infected by mosquitoes acquire virus infection or mosquitoes bite while feeding on WNV infected birds. About 20% of WNV infected individuals develop symptoms after incubation period of 3-14 days. The comman symptoms of WNV are headache, fever, rashes, nausea and vomiting etc. But this situation become critical during neurological complications like encephalitis, meningitis and acute flaccid paralysis occurs in young or old age individuals