The recognition of hepatitis E as a discreet disease entity in the late 1970s followed the development of serological tests for hepatitis A and the discovery that large waterborne outbreaks of hepatitis in India were not caused by hepatitis A virus (HAV). These "enterically transmitted non-A, non-B hepatitis" outbreaks had distinctive epidemiologic features, including the highest attack rates among young adults, little secondary household transmission of infection, and severe disease in pregnant women. The responsible agent, hepatitis E virus (HEV), was identified several years later in extracts of feces from a self-inoculated virologist. Multiple genetically related HEV genotypes are now known to exist, two of which are common in domestic swine herds and the cause of sporadic cases of acute hepatitis in economically well-developed countries. HEV genotypes possess impressive genetic and biologic diversity, and present many unanswered questions concerning their natural host range, potential for zoonotic transmission, and disease pathogenesis.