Our basic understanding of the biology, molecular virology, and immunology of hepatitis E virus (HEV) is briefly reviewed. HEV is a small, round, nonenveloped virus with morphologic and biophysical properties most similar to viruses found in the family Caliciviridae. The genome of HEV is approximately 7.5 kb in length and consists of a positive-sense, single-stranded RNA molecule that contains three distinct open reading frames (ORF1, ORF2, ORF3) that appear to encode for nonstructural and structural proteins based on the presence of well-defined consensus motifs and genomic organization similar to those of other calici- or calici-like viruses. Limited epitope mapping of the viral genome with synthetic peptides has revealed the presence of highly immunoreactive type-common and type-specific epitopes; these finding are consistent with the results of other studies that used recombinant expressed proteins from both the nonstructural and structural regions of the derived viral proteins encoded by ORFs 1, 2, and 3. Synthetic peptides and recombinant expressed proteins have been used to develop Western blot assays and enzyme immunoassays (EIAs) for the detection of IgA, IgG, and IgM anti-HEV in human and primate sera. Knowledge of the dynamics of HEV antigen and antibody expression in experimentally-infected primates is emerging, and prototype vaccines have been developed with recombinant expressed ORF2 and ORF3 proteins. Limited seroprevalence studies of anti-HEV in endemic and nonendemic regions of the world using one or more of the above assays has revealed a strong correlation between level of sanitation and incidence of disease and prevalence of anti-HEV.