Hepatocellular carcinoma (HCC) is a major contributor to cancer incidence and mortality. There is a wide variation, however, in the global distribution of HCC. Eighty percent of the burden is borne by countries in Asia and sub-Saharan Africa. In most high-risk countries, principal risk factors include infection with hepatitis B virus and dietary exposure to aflatoxin B(1). In contrast, hepatitis C virus and alcohol consumption are more important risk factors in low-risk countries. In recent years, the incidence of HCC has decreased in some high-risk countries and increased in some low-risk countries. Reasons for both trends are not completely understood, but are likely related to public health efforts in Asia and the increase in hepatitis C virus infection in low-risk countries. Vaccination programs against hepatitis B virus will likely decrease the HCC rate even further in decades to come.