Eastern equine encephalomyelitis (EEE) virus belongs to the genus Alphavirus of the family Togaviridae. EEE virus is present in the Americas and can cause disease in both humans and equids with encephalitis in most clinical cases. EEE virus is typically maintained in nature by alternating between vertebrate hosts and vector mosquitoes. Encephalitis caused by this virus occurs sporadically in horses and humans from mid-summer to late autumn in temperate regions but can occur year-round in tropical regions, depending on climate conditions that support the presence of the mosquito vector. Clinical disease in horses is characterised by fever, anorexia, and depression. In severe cases, it can progress to hyperexcitability, blindness, ataxia, severe mental depression, recumbency, convulsions, and death. EEE virus infection in horses is often fatal. The principal reservoir hosts for the virus are passerine birds. Most infections in birds are nonclinical, but EEE virus has been reported to cause disease in poultry, game birds and ratites. Small mammals, such as rodents may also amplify EEE. Sporadic cases of EEE have been reported in cows, sheep, pigs, deer, and dogs. Horses and humans are incidental dead-end hosts for EEE virus. However some horses may develop a transient viraemia that has been suggested to be sufficient to transmit EEE virus to mosquitoes under the right conditions. EEE vaccines are safe and immunogenic.