The systemic chemotherapy of hepatocellular carcinoma with single agent or combination chemotherapy has not resulted in reproducible response rates above 20%. Correspondingly, an effect on the survival of the treated patient population has not been shown so far. The most effective single agent is doxorubicin, which should, however, not be used outside of clinical studies in the systemic treatment of hepatocellular carcinoma. The results of hormonal treatment of hepatocellular carcinoma are also disappointing: the response rates of agents like tamoxifen, ketoconazol, nilutamid, LHRH-agonists or megestrol are usually below 10% and the survival of patients can not be improved. New approaches that are currently tested in vitro and in mouse models are pharmacological or immunological interactions with tumor cells that make use of molecular biology techniques and are summarised under the term "gene therapy". Some of these projects are in clinical phase I studies and first results can be expected in the next three to five years.