Primary hepatocellular carcinoma is a rare malignancy but its incidence has increased over the last decade. Only a few patients have resectable tumours at presentation. The prognosis in the large majority of the cases is poor with a life expectancy of a few months. In this article we have reviewed the different medical approaches tested in this neoplasm. The results are disappointing. Over the next ten years much effort will be needed to improve both treatment and prognosis while investigations need to be carried out in collaboration with experimental laboratories. We are therefore presenting the possible pathways for future research.