Hepatitis B virus (HBV) infection usually leads to self-limited acute hepatitis with complete recovery of the patients and clearance of the virus from the circulation. However some patients (5 to 10%) do not clear the virus and they become chronic carriers, with or without evidence of liver disease. The sequence of events leading to clearance or persistence of HBV in the infected organism are still largely unknown. Based on available data derived from studies in HBV and in other viral systems, it is generally assumed that a human leucocyte antigen (HLA) class I-restricted cytotoxic T lymphocyte (CTL) response to one or more HBV-encoded antigens displayed at the hepatocyte membrane is a major effector mechanism of hepatocellular injury and clearance of infected cells. Elucidation of the immunological and virological basis for HBV persistence may yield immunotherapeutic strategies to terminate chronic HBV infection.