Hepatitis E infection, caused by the hepatitis E virus (HEV), is a common cause of acute hepatitis in developing countries with poor sanitation and hygiene. The virus is classified into four genotypes (1-4) with one serotype. Genotypes 1 and 2 exclusively infect humans, whereas genotypes 3 and 4 also infect other animals, particularly pigs. In endemic areas, large outbreaks of acute hepatitis caused by viruses of genotype 1 or 2 frequently occur due to fecal-oral transmission, usually through contamination of drinking water. With a high attack rate in young adults (aged 15-45 years), the disease is particularly severe among pregnant women (20-30% mortality). HEV appears to be a zoonotic disease, with transmission from pigs, wild boars, and deer, or foodborne. Chronic infections are rare, except in immunosuppressed persons, such as organ transplant recipients. A subunit vaccine has been shown to be effective in preventing the clinical disease, but is not yet commercially available. Our understanding of HEV has undergone major changes in recent years and in this article we review the currently available information with regard to the molecular biology, pathobiology, and epidemiology of HEV infection. We also review the current therapeutic interventions and strategies being used to control HEV infection, with emphasis on possible approaches that could be used to develop an effective vaccine against HEV. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.