Delta hepatitis or hepatitis D leads to acute and chronic liver disease in humans. The causative agent, the hepatitis delta virus (HDV), is a defective virus which leads to hepatitis in humans in the presence of the hepatitis B virus. This helper function of HBV is required for transmission and propagation of HDV infection but not for replication. HDV RNA replication occurs through the double-rolling circle model and does not possess a reverse transcription step. Hepatitis D-induced liver disease is immune-mediated and occurs either as co-infection of both viruses or as superinfection of a hepatitis B carrier with hepatitis D. Based on a sequence variation of 19-38%, to date seven genotypes of HDV have been described. HDV infection has declined significantly in many endemic areas in the last decades, however, due to migration to industrialized countries, this decline appears to have reached a plateau in western countries. The clinical course of delta hepatitis in general is associated with rapid progression. Delta hepatitis may be an additional risk factor for the development of hepatocellular carcinoma. The only established management for delta hepatitis consists of treatment with interferon for a period of at least one year. For those unresponsive to interferon treatment and patients with advanced disease new therapies are an urgent need. Such therapies may be on the horizon but translation of bench work to clinical practice is required.