Hepatocellular carcinoma is a very prevalent malignancy worldwide, with increasing incidence in the United States. Despite many available treatment options, the prognosis remains poor. Surgical resection or liver transplantation still represents the only potentially curative treatments for HCC. Until more effective systemic therapies are available, different localized treatment approaches will continue to be applied in the management of this disease. Although systemic chemotherapy has been disappointing, increased understanding of the tumor biology in HCC coupled with new drug development may lead to newer agents with novel mechanisms of action that are more efficacious. The poor treatment outcome and dismal prognosis make prevention of HCC an important strategy in controlling this aggressive type of malignancy. Vaccine programs for HBV are ongoing. Efforts are underway to develop a vaccine for HCV. Interferon therapy appears to decrease the risk of developing HCC in patients with hepatitis, especially those with HCV. A number of other approaches for decreasing risk in these patients as well as in those with alcoholic-related cirrhosis are currently being evaluated.