Abstract:Hepatitis B virus (HBV) is quite successful in vertical transmission in the human host by induction of immune tolerance. It has a tiny but quite compact genome with overlap not only between genes but also between coding and non-coding sequences. How such a complex virus evolved from its more primitive ancestor remains unknown， but the presence of related hepatotropic DNA viruses (hepadnaviruses) or integrated genomic DNA in birds， amphibians， crocodiles， snakes， turtles and mammals suggest an old origin. Today the HBV isolates worldwide can be classified into 8 distinct genotypes. In addition， the transition from immune tolerance phase to the immune clearance phase of chronic infection triggers the replacement of wild-type virus by a series of mutants. This review article will start with an overview of the HBV lifecycle， followed by discussion of the role of viral genotypes and specific mutations on the establishment of chronic infection， development of fulminant hepatitis， or hepatocellular carcinoma. We end by comparing HBV with other members of hepadnaviruses to shed light on its recent evolutionary history.