Hepatocellular carcinoma (HCC) is one of the most common tumors affecting man. It is the general feeling that only hepatectomy can give a chance for cure. However, less than 20% of patients can be resected, and other treatment modalities are required. Systemic (chemotherapy, hormonotherapy, immunotherapy) and loco-regional (intratumoral injection of alcohol, intra-arterial chemotherapy embolization, internal radiotherapy) approaches have been developed. In view of the small number of patients, tumor and patient heterogeneity, and difficulties in assessing tumor response, the real place of these treatments is difficult to evaluate. A review of the literature suggests that embolization with Gelfoam, even when given without chemotherapy, has an effect on response rate and on survival, and could be considered, at the present time, as the most attractive treatment in non-operable HCC. Chemotherapy seems effective only if combined with embolization. When administered alone by the systemic or the intra-arterial hepatic route, no clinically significant activity can be found. Unexpectedly, Lipiodol by itself seems inactive, and the co-administration of chemotherapy does not improve activity. Other approaches such as intratumoral injection of alcohol, immunotherapy, hormonotherapy, and radioimmunotherapy are still experimental, and well-designed studies are needed to identify their role.