Many viruses may cause encephalitis. Three such viruses of the Alpha genus (Venezuelan equine encephalitis (VEE), Western equine encephalitis (WEE) and Eastern equine encephalitis (EEE)) may be used as biological warfare agents. The clinical course of the diseases caused by these viruses is not specific, and resembles a broad range of bacterial and viral diseases. Several attenuated and inactivated vaccines were developed, but their efficacy in the biological warfare scenario is questionable. There is no effective drug therapy for the treatment of these diseases, and treatment is mainly supportive. Several VEE outbreaks were reported in humans and horses in South America and southern United States. This virus usually causes a febrile illness, which might be complicated with encephalitis, mainly in the cases of children and elderly patients. The EEE virus causes the most severe form of disease, with severe encephalitis and high proportion of sequel. It is prevalent mainly in the eastern parts of Northern America. The WEE virus, which is hybridization between the Sindbis virus and the EEE virus, causes encephalitis mainly in children. The severity of the disease caused by WEE and the sequel rate is much lower than that of EEE.