The presence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg)-negative individuals is defined as occult HBV infection (OBI). OBI is related in some cases to infection with variant viruses (S-escape mutants) undetectable by HBsAg commercial kits. More frequently, however, it is due to infection with wild-type viruses that are strongly suppressed in their replication activity. OBI may be involved in different clinical contexts, including the transmission of the infection by blood transfusion or liver transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it may contribute to the development of cirrhosis and may have an important role in hepatocarcinogenesis.