Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and is estimated to cause approximately half a million deaths annually. Because of its high fatality rates, the incidence and mortality rates are almost equal. The major risk factors for HCC are chronic hepatitis B virus infection, chronic hepatitis C virus (HCV) infection, and alcoholic cirrhosis. The epidemiology of HCC is characterized by marked demographic (age, gender, race/ethnicity) and geographic variations. Hepatitis B virus infection, with and without aflatoxin exposure, is responsible for most cases in developing countries; better control of these risk factors has resulted in a recent decline in HCC in some places like Taiwan and China. Recently, however, a trend of rising rates of HCC has been reported from several developed countries in Europe and North America. These new trends are associated with "new" risk factors such as HCV and, possibly, diabetes. In the United States, the incidence of HCC has approximately doubled over the past 3 decades. White individuals are two to three times less often affected than African Americans, who in turn are two to three times less often affected than Asians, Pacific Islanders, or Native Americans. Men are two to three times more often affected than women. Concomitant with the rising rates of HCC, there has been a shift of incidence from typically elderly patients to relatively younger patients between ages of 40 to 60 years. An increase in HCV-related HCC accounts for at least half of the witnessed increase in HCC in the United States. Hepatocellular carcinoma continues to carry an overall dismal survival rate (close to 5%); very few patients qualify for and receive potentially curative therapy. The future incidence trends of HCC will be determined to a large extent by the clinical course of HCV-infected people.