Hepatitis E virus (HEV) is the aetiological agent of non-HAV enterically transmitted hepatitis. It is the major cause of sporadic as well as epidemic hepatitis, which is no longer confined to Asia and developing countries but has also become a concern of the developed nations. In the Indian subcontinent, it accounts for 30–60% of sporadic hepatitis. It is generally accepted that hepatitis E is mostly self-limited and never progresses to chronicity. It has a higher mortality in pregnant women where the disease condition is accentuated with the development of fulminant liver disease. Currently, no antiviral drug or vaccine is licensed for HEV, although a vaccine candidate is in clinical trials. HEV genome is 7.2kb in size with three open reading frames (ORFs) and 5′ and 3′ cis acting elements, which have important roles to play in HEV replication and transcription. ORF1 codes for methyl transferase, protease, helicase and replicase; ORF2 codes for the capsid protein and ORF3 for a protein of undefined function. HEV has recently been classified in the genus Hepevirus of the family Hepeviridae. There are four major recognised genotypes with a single known serotype. The absence of a reliable in vitro propagation system is an obstacle to deciphering HEV biology. The genome of HEV has been cloned, sequenced and the infectious nature of these replicons has been established. However, questions related to replication, transcription, virus-host interactions and pathogenesis remain to be answered. This comprehensive review summarises the progress made so far in HEV research, and addresses some of the unanswered questions. Copyright © 2006 John Wiley & Sons, Ltd.