Nowadays, renal cell carcinomas (RCC) are mostly detected incidentally, following abdominal ultrasound performed for non-urological complaints. These asymptomatic tumors are often small and with low stage. However, about 25% of the RCC are still detected in advanced stage, with synchronous metastasis. Since few years ago, there was no effective treatment for the advanced RCC that shows resistance to the traditional systemic chemotherapy and radiotherapy. Today, two different treatments, either alone or in association, have provided interesting results in these setting, mostly in term of stabilization of the disease. Continuous systemic chronobiological chemotherapy with Floxuridine and immunotherapy with recombinant Interleukin-2 administered intravenously or subcutaneously, represent the treatment of choice of advanced RCC. Both treatment are well tolerated by the patients (except the intravenous Interleukin-2) and do not preclude radical nephrectomy. This paper reports a review of recent literature and the results of the authors' experience.