Renal carcinoma represents about 3% of all adult tumors, with an estimate of 31,900 new cases diagnosed in 2003 in the United States. In the early phase of its natural history, renal cancer is potentially curable by surgery, but if the disease presents any signs of metastasis, the chances of survival are remote, even though anecdotal cases characterized by long survival have been reported. In fact, the treatment of metastatic renal cancer remains unsatisfactory. Systemic treatment with single agents and with polychemotherapy, with or without cytokine-based immunotherapy, has not been successful, obtaining very low response rates without a significant benefit in overall survival. This review highlights the most interesting issues regarding conventional therapeutic strategies, in localized and in advanced disease. New approaches such as monoclonal antibodies, vaccines, gene therapy, angiogenesis inhibitors and allogeneic cell transplantation and their possible clinical applications are also discussed.