Unfortunately, in most large treatment centers that see a large volume of HCC patients, less than 10% are candidates for surgical treatment. The reasons for exclusion from surgical treatment may include presentation with advanced-stage or metastatic disease, major vascular invasion by tumor, paucity of organs for transplantation, and severity of cirrhosis too great to permit surgical treatment. There have been numerous types of regional and systemic therapies used to treat HCC in patients who are not candidates for surgical treatment. This is a highly resistant and aggressive disease and sadly very few patients who are not candidates for surgical treatment survive more than 2 years, much less having a chance at 5-year survival. Worldwide, the overall mortality rate for HCC in all patients exceeds 94%, so it is clear that better screening programs to diagnose patients at an earlier stage of disease would be highly desirable. It is not clear if such screening programs would be cost effective but this will become an issue due to the increased incidence of this disease in both modern and less developed regions of the world. Similarly, programs aimed at prevention of disease are crucial. Hepatitis B vaccinations have made an impact on the incidence of this cancer in portions of the world where chronic hepatitis B infection is hyperendemic. There is no vaccine for hepatitis C and this virus is supplanting hepatitis B virus as the most common cause of HCC worldwide. Education and prevention are important factors, but clearly better treatments are also needed for this lethal disease. Currently the oral agent sorafenib, a multiple tyrosine kinase inhibitor, has become a standard therapy for patients with advanced and unresectable HCC. However, use of sorafenib enhances survival by an average of less than 3 months, so more effective therapeutic agents for patients with advanced disease must be sought and developed.