Hepatitis E virus (HEV) infection has been considered a disease associated with developing regions and attributed to oral-fecal transmission due to inadequate sanitation. Several recent findings, however, have led to a new understanding of this virus. A number of novel isolates have been identified in patients with acute hepatitis from regions not considered endemic for HEV, and these individuals reported no recent travel to HEV endemic areas. In addition, a number of HEV-like sequences have also been isolated from swine worldwide, suggesting the potential of an animal reservoir. Although full-length sequence is available for some strains, the majority of HEV isolates have only been sequenced partially. Sequence comparisons and phylogenetic analyses were performed to determine the genotypic distribution of HEV isolates, based on the partial sequence data available. It has been suggested that HEV isolates segregate into four major genotypes based on full-length comparisons. These analyses, however, indicate that HEV may be distributed into at least nine different groups. J. Med. Virol. 65:282–292, 2001. © 2001 Wiley-Liss, Inc.