Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing countries in Asia and Africa, where it is transmitted by the fecal–oral route because of poor sanitation practices. Acute hepatitis E is also increasingly reported in industrialized countries, where the transmission is mainly zoonotic. The initial discovery of HEV transmission from domestic pigs has been followed by evidence that other mammals, such as wild boars, ferrets and deer, are also potential reservoirs of HEV. The virus is spread by ingesting contaminated food (venison, pork, or shellfish) or water. In the United States antibodies to hepatitis E virus are more prevalent among veterinarians who work with pigs than other people. Recent studies have characterized new HEV types from rats in Germany, wild boars in Japan, and farmed rabbits in China and Netherlands. HEV was also recently found in farmed rabbits in Virginia, USA. Although the course of HEV infection is generally without symptoms (or symptomatic with acute hepatitis), fulminant hepatitis can occur in pregnant women and in persons with underlying liver disease. Farmed and wild rabbits are naturally infected with HEV. The distribution of HEV in the tissues of infected wild rabbits showed HEV RNA not only in the liver, but also in the intestine and cecum. Because the human HEV strain is closely related to rabbit HEV strains, this finding thus supports the potential of zoonotic transmission from rabbits to humans.