Chronic infection with the hepatitis B virus has been linked epidemiologically to the development of hepatocellular carcinoma for more than 30 years. Although the mechanisms by which chronic hepatitis B viral infection results in hepatocellular carcinoma are unclear, there is good evidence that the virus itself exerts a direct hepatocarcinogenic effect, and this has implications for prevention. First, programs of universal infant vaccination have been shown to be effective in reducing the rate of hepatocellular carcinoma among children. This benefit should be translated into adulthood among vaccine recipients. Second, it has been suggested that antiviral therapy against hepatitis B may reduce the risk of hepatocellular carcinoma. Antiviral therapy against hepatitis B is effective in causing prolonged lowering of serum levels of hepatitis B virus DNA. There are emerging data showing that prolonged antiviral therapy may reduce the risk of hepatocellular carcinoma among certain patients with chronic hepatitis B.