Equine encephalosis (EE) is an arthropod-borne, febrile, noncontagious disease of equines, initially referred to as equine ephemeral fever by Theiler in 1910 [1]. The causal agentequine encephalosis virus (EEV)—was rst identied in 1967 in South Africa from a thoroughbred mare displaying marked neurological signs, including listlessness, tightening of the muscles of the face, high temperature, and elevated pulse rate about 24  h before death. Transmitted by Culicoides biting midges, the virus was also isolated from the blood samples of other horses located nearby, which showed no overt clinical signs apart from a febrile reaction [2]. Although EEV is capable of causing <5% mortality in affected animals, it is noninfective to humans and thus poses no public health risk. The real signicance of EEV infections lies in the fact that the mild forms of EE are clinically similar to those of African horse sickness (AHS), which is caused by African horse sickness virus (AHSV) (see Chapter 68). AHSV utilizes identical vectors for transmission and represents one of the most devastating equine pathogens. It is, therefore, important to differentiate EE from AHS, so that tailor-made strategies are implemented for effective control and prevention. In this chapter, we focus on EEV in relation to its classication, morphology, genome organization, epidemiology, clinical features, and diagnosis.