Until 1 year ago, immunotherapy was considered the standard treatment of metastatic renal cell carcinoma (MRCC) producing objective response of 10%-20% and an overall survival of approximately 1 year. Recently, some multitarget-oriented drugs have shown an impressive activity in MRCC with a high percentage of partial response and/or stable disease with a significant impact on survival. Nevertheless, immunotherapy remains another important therapeutic option for these patients. The value of immunotherapy is its curative potential in some patients and its capability to obtain very durable responses as demonstrated by long-term follow-up. Interesting results seem obtained also when immunotherapy is used in combination with some chemotherapeutic agents. Gemcitabine demonstrated be a good drug to combine with immunotherapy because of its little detrimental effects on cellular immunity. In phase II studies, interesting results have been reported. We treated 41 patients with MRCC using a biweekly schedule including s.c. interleukin 2 (IL-2), gemcitabine and vinorelbine. The overall response was 40% and the median survival was 24 months. Treatment was well tolerated and easily manageable. Vaccines are another promising treatment of RCC intended to stimulate a specific antineoplastic response. Vaccines have been explored both in an adjuvant and in a metastatic setting. We started a pilot study with dendritic cells vaccine loaded with autologous tumor in MRCC. The treatment has resulted feasible, well tolerated and effective in a minority of patients. In the future, combination immunotherapy with multitarget-oriented drugs may be one way forward. Also advances in cellular therapies and new immunomodulatory molecules as monoclonal antibodies are producing new therapeutic options. Finally, the identification of a panel of prognostic factors could provide an important tool to guide the choice of treatment of patients with a different risk profile. Therefore, the increasing therapeutic options for RCC should be seen not as a competition among the different treatments but as an expanding armamentarium available for these patients.