A large number of viruses are capable of inducing acute or chronic hepatitis. The syndrome of chronic hepatitis encompasses not only viral but also autoimmune liver diseases. The hepatitis C virus, and recently also the hepatitis D virus have been found to be associated with an array of autoimmune syndromes, diseases and markers of autoimmunity. The relationship of hepatotropic virus infection and the immune system leading to virus-associated autoimmunity, and its distinction from genuine autoimmune disease represents a fascinating field of research. Clinically, the differentiation between autoimmune liver diseases, virus infection and virus-associated autoimmunity is difficult and epidemiological evaluations have not come up with universally applicable and valid classification criteria. However, both autoimmune liver diseases and viral hepatitis can readily be diagnosed and distinguished through precise and molecularly determined immunological testing systems. The overlap of both, virus-associated autoimmunity, is still at the centre of research activities aimed at establishing diagnostic and risk-assessment criteria. Studies of molecular autoantigens and autoepitopes have begun to define the differences of the B-cell response in autoimmune disease and virus-associated autoimmunity. This provides data that may contribute to the safe application of therapeutic strategies as different as immunosuppression and interferon-alpha (IFN-alpha). The present review focuses on the clinical, epidemiological and molecular aspects of these disease entities.