Thirty years after its discovery, the hepatitis B virus (HBV) still remains a major global public health problem. Worldwide, two billion subjects have been infected, 300 million have a chronic infection and more than 600,000 die annually of HBV-related liver disease or hepatocellular carcinoma; new infections occur because of the presence of a large reservoir of chronic carriers of the virus. The knowledge of the HBV organization and replication cycle and the availability of sensitive HBV-DNA assays have led to remarkable progress in our understanding of the natural history of chronic hepatitis B infections. Crucial to the prevention of new infections, to the management and the monitoring of HBV carriers and to the choice of best treatment strategy, is the understanding of the natural dynamism of HBV infection and of the virus-host interactions that induce liver damage.