Hepatocellular carcinoma represents one of the most important tumor entities worldwide. The great majority of these cases in Germany can be attributed to chronic liver disease (alcohol, viral hepatitis among others), which lead to development of liver cirrhosis and ultimately to hepatocellular carcinoma. While our understanding of the pathophysiological principles underlying the origin of hepatocellular carcinoma has increased considerably in recent years, the prognosis of the majority of these patients remains poor. However, a combined interdisciplinary approach involving internists, surgeons, and radiologists can often achieve effective palliative treatment of the disease. This has recently been reinforced by applying systemic therapies which specifically influence the important biological processes of hepatocellular carcinoma. It can be assumed that by adhering to well-defined treatment algorithms and using improved drug therapy the prognosis of patients with this form of cancer will improve in the future.