The persistence of hepatitis B virus (HBV) genomes in HBV surface antigen (HBsAg) negative individuals is termed occult HBV infection. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays, but more frequently it is due to a strong suppression of viral replication and gene expression. Occult HBV infection is an entity with world-wide diffusion, although the available data of prevalence in various categories of individuals are often contrasting because of the different sensitivity and specificity of the methods used for its detection in many studies. Occult HBV may impact in several different clinical contexts, including the transmission of the infection by blood transfusion or organ transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it can favour the progression of liver fibrosis and above all the development of hepatocellular carcinoma.