Renal cell carcinoma is a chemotherapy-resistant tumor, which, with commonly used cytotoxic agents, exhibit a only marginal response rate when modern objective response criteria are applied. No clear survival benefit for patients treated with chemotherapy has yet been demonstrated, although most trials indicate that responding patients survive longer. Among the more commonly available cytotoxic agents, vinblastine has been repeatedly reported to achieve a 6-9% objective response rate irrespective of the mode of application. 5-fluorouracil- and Floxuridin (FUDR)-based chemotherapy appear to achieve response rates in the range of 5-8%, with slightly better results when applied by chronomodulation schedules. Trials evaluating the recently licensed newer cytotoxic agents have shown no major improvement for the treatment of metastatic renal cell cancer. Studies including the topoisomerase I inhibitors irinotecan and topotecan are ongoing. The taxanes (paclitaxel, docetaxel) have demonstrated no significant activity and gemcitabine has been reported with responses in single patients. Recent treatment approaches based on the biology of renal cell carcinoma with an increased expression of the multiple drug resistance (MDR) phenotype (pgp 170) have used chemotherapy in combination with verapamil or cyclosporine derivates as inhibitors of the MDR-mechanism. The disappointing results of these trials indicate that MDR is not the only mechanism of chemotherapy-resistance in renal cell carcinoma. In conclusion, chemotherapy has a limited role in metastatic renal cell carcinoma and vinblastine is considered the standard treatment. Strict evaluation of new agents acting independently from the MDR-mechanism is necessary in order to identify drugs with an impact in the palliative treatment of advanced renal cell carcinoma.