The hepatitis D virus (HDV) or delta agent is a defective RNA virus that requires HBV infection to complete its replication. Thus, HDV infection only occurs with simultaneous HBV co-infection or by super-infection of someone chronically infected with HBV. Acute HDV infection acquired by co-infection with HBV can range from mild to severe hepatitis and is clinically indistinguishable from acute hepatitis B. With super-infection, there is clinically a more severe acute hepatitis and because of the underlying persistent HBV infection, HDV infection generally is associated with more rapidly progressive liver disease and an increased risk of hepatocellular carcinoma. HDV infection is endemic worldwide but with the control of HBV infection by vaccination, the prevalence of HDV infection has declined substantially over the last twenty years.