The median survival of patients with metastatic bladder cancer treated with methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy is approximately 1 year and long-term survival occurs in a small proportion of patients. Recent efforts to improve the outcome of patients with metastatic transitional cell carcinoma have focused on the identification of new drugs with single agent activity and on their incorporation into platinum-based combination regimens. Paclitaxel, docetaxel, ifosfamide and gemcitabine are among the most active new agents. A large number of phase I/II trials have evaluated these agents in two- and three-drug combination regimens. The response proportion observed with these combinations varies considerably and median survival times range from 8 to 20 months. Because it is known that pretreatment prognostic features have an impact on individual patient outcome, the variation in reported survival in patients treated with chemotherapy may be a consequence of pretreatment patient characteristics. The role of surgery in metastatic bladder cancer is still controversial. After a significant response to chemotherapy, resection of residual resistant disease may be performed with intent to cure in highly selected patients. As obtainment of complete remission is a prerequisite for long-term survival, new therapeutic strategies, such as molecular targeted small molecule therapy and monoclonal antibodies, and new molecular markers predictive of response have the potential to be incorporated into the current treatment strategies, increasing the rate of cure.