Hepatitis E, previously known as enterically transmitted, enteric, or epidemic hepatitis, is a worldwide public health problem. The causative agent, the hepatitis E virus, is involved in epidemic, sporadic, and fulminant hepatitis cases worldwide. This review describes the advances in the biology of the hepatitis E virus and the progress made to develop simple and robust serologic assays for the diagnosis of HEV infection. Genomic sequence comparisons with a recently identified US isolate now suggests three genetic groups of HEV viruses. A highly conserved animal isolate found in pigs suggest the coexistence of animal and human isolates of HEV. The use of recombinant technology to develop an effective subunit vaccine capable of providing cross-protection for the most divergent HEV strains has been established and is reviewed.