The causative agent of hepatitis delta virus (HDV) is the most unusual of all causative agents for all hepatitis viruses. Current knowledge of the molecular biology of HDV strengthens its proposed classification within the satellites, a family of subviral agents, some of which are pathogens of higher plants. Hepatitis delta virus is the only virus in the satellite family known to infect animal species, with hepatitis D having affected more than 10 million people worldwide who are also infected with its helper virus, HBV. Recently, the world map for hepatitis D appears somewhat modified, with decreasing HDV prevalence in certain areas and some new foci of HDV endemicity. Despite changing HDV prevalence, hepatitis D, particularly the chronic form, is still an important health problem worldwide in terms of morbidity and mortality (mainly due to chronic liver disease, including hepatocellular carcinoma). Molecular studies have greatly advanced our understanding of the life cycle of HDV and of the function of its proteins. The new molecular information is of clinical relevance, with implications for the pathogenesis of liver damage, the diagnosis of HDV infection, for the natural course of the disease and, potentially, for therapy. Sensitive assays for HDV-RNA by polymerase chain reaction and sequencing techniques have clarified the patterns of HDV transmission and have confirmed the existence of unusual clinical forms of the virus and their relationship to replicative levels and genotypes of HDV. Prevention and treatment of hepatitis D are still in their infancy. However, liver transplantation for delta cirrhosis has proven far more successful than in any other viral form of cirrhosis, with few reinfections of the grafted liver, and has given important information on HDV biology and the pathogenesis of liver damage.