It has been recognized for some time that there is a strong link between infection with the hepatitis B virus (HBV) and the development of hepatocellular carcinoma (HCC). HBV was one of the first viruses to be associated with a human cancer, and the retroviruslike nature of HBV provided a natural link with animal models of cancer caused by various retroviruses. Nearly 20 years ago, these similarities were confirmed with the discovery of HBV DNA integrated within the DNA of human liver and HCC tissue. This was supported by strong epidemiologic data linking current or previous HBV infection with HCC, and cell culture evidence such as the establishment of a human HCC cell line containing integrated HBV DNA and producing hepatitis B surface antigen (HBsAg). The woodchuck animal models in which woodchucks are infected with an agent very similar to human HBV and frequently develop HCC, further supports the link. More recently, efforts have concentrated on trying to understand the mechanisms of HBV-related hepatocarcinogenesis and on implementing large-scale HBV vaccine programs to prevent this common form of cancer.