Hepatitis E was considered to be endemic infectious disease in developing countries in tropical or subtropical regions with poor sanitary conditions. Large, previously reported outbreaks were mainly due to contaminated water or heavy flooding. Prototype hepatitis E viruses of genotypes I and II were obtained from such endemic cases. In developed countries, in contrast, hepatitis E was rare and diagnosed only in travelers or imported cases. However, the development of accurate diagnostic tests, mainly PCR detection elucidated that autochthonous hepatitis E in developed countries is far more common than previously thought. Although the main route of transmission is food-borne, other routes including blood-borne have been suggested. Recent developments of gene-based diagnostic assays and molecular epidemiology have disclosed the significance of hepatitis E virus infection in developed countries.