This article considers the implications of recent advances in hepatitis delta virus (HDV) research on understanding HDV disease and its pathogenesis. Particular emphasis is placed on the potential effects of HDV genotypic variations on disease. It is clear now that HDV infection is associated with a very broad spectrum of acute and chronic liver disease. The recognition of distinct genotypes of HDV that are associated, in some cases, with different disease patterns is a particularly promising development for the understanding of disease variations and mechanisms. Other topics of discussion include the influence of hepatitis B virus on HDV infection and triple infection with hepatitis C virus and HIV.