Hepatitis B virus (HBV) affects more than 300 million individuals worldwide and in the United States approximately 1.25 million individuals are chronic carriers of HBV. The risk of becoming a chronic hepatitis B virus surface antigen carrier is dependent upon the mode of acquisition of infection as well as the age of the individual at the time of infection. For those individuals with high levels of viral replication, chronic active hepatitis with progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC) is common and liver transplantation is an excellent treatment option for patients with end-stage liver disease from HBV. Patients with chronic HBV infection should be screened periodically for hepatoma, although screening strategies have not been proven to prolong survival. Newer antiviral agents for the treatment of HBV are potent inhibitors of HBV-DNA and their long-term effect on the natural history of HBV is yet to be proven. The natural history of hepatitis C virus (HCV) infection is less well defined than that of chronic HBV. Certain patients who are chronic carriers of HCV may never develop extensive fibrosis, whereas others will progress to chronic active hepatitis with cirrhosis, HCC and end-stage liver disease. Factors that influence the progression of HCV are those related to the host, including the age at acquisition of infection, gender and immune status, and the disease process is accelerated in patients who consume regular amounts of alcohol. Hepatocellular carcinoma develops frequently in patients with HCV infection and its overall incidence is increasing due to this chronic viral disease. Patients with HCV cirrhosis should be screened regularly for hepatoma and liver transplantation is an effective treatment option for those with end-stage disease. The impact of antiviral therapy on the natural history of HCV is still to be determined and should be the focus of large clinical trials.