Occult hepatitis B virus (HBV) infection is a peculiar form of chronic viral infection identified since the early 80's and can be defined as the presence of HBV DNA in the serum and/or in the liver tissue of patients negative for the HBV surface antigen (HBsAg) using usual serological tests. The data about the prevalence of occult HBV infection are contrasting and the reported prevalences in various categories of individuals are highly diverse. The molecular basis of the occult HBV infection is the covalently closed-circular DNA (cccDNA) that persists in the cell nuclei and that serves as a template for gene transcription. The physiopathology of occult HBV infection is still unclear. However, the available data suggest that the host's immune response, the co-infections with other infectious agents and epigenetic factors may play important roles in indicing the occult status. The clinical relevance of occultHBVinfection remains debated but it may impact in four clinical contexts: 1) the transmission of the infection by blood transfusion or organ transplantation; 2) the acute reactivation when an immunosuppressive status occurs mainly in patients with isolated anti-HBc (chemotherapy, transplantations, immunodepression, new immunosuppressive therapy as anti-CD20 or anti TNF); 3) the potent but non proved progression of liver fibrosis in HCV infected patients or in patients with cryptogenetic liver disease; and, 4. the risk factor for hepatocellular carcinoma development.