Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are among the most frequent viral infections in humans, and represent a major global public health problem. HBV- and HCV-related chronic hepatitis are the main causes of cirrhosis and hepatocellular carcinoma (HCC) that are responsible for a high rate of morbidity and mortality. End-stage HBV- and HCV-related liver disease and HCC are the main causes of liver transplantation. In the last few years, knowledge of the epidemiology and the natural history of HBV and HCV infection has markedly improved. Furthermore, considerable progress has been made in the efficacy of therapy. New drugs and new therapeutic strategies that are currently under evaluation could further improve the efficacy of therapy in the near future.