Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for HCC development are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. The therapeutic options fall into five main categories: (1) surgical interventions, incl. liver transplantation, (2) percutaneous interventions, incl. ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, (4) radiation therapy and (5) drugs as well as gene and immune therapies. Because of the poor survival of the majority of patients, HCC prevention as well as early diagnosis and the development of novel systemic therapies for advanced disease are of paramount importance. In this context, recent data indicate that the 'targeted therapy' with monoclonal antibodies (mabs) or small molecule tyrosine kinase inhibitors (nibs) and other drugs seem to be effective to some degree. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.