Carcinoma of the bladder is the second most prevalent genitourinay malignancy and the fifth most common solid tumor in the USA. On the basis of favorable response rates and survival data, cisplatin-based regimens can be considered the standard treatment for fit patients with metastatic urothelial cancer. Since cisplatin-containing regimens are contraindicated for patients with impaired renal function, gemcitabine plus either paclitaxel or docetaxel may be an effective and well-tolerated treatment option for these patients. Randomized trials are needed to determine the future role of these combinations in the management of advanced transitional cell carcinoma. The optimal regimens for the medically unfit patients and second-line chemotherapy remain undefined. Postchemotherapy surgical resection of residual cancer may result in a disease-free survival in highly selected patients who would otherwise die of the disease. Progresses in the understanding of the molecular biology of bladder cancer and identification of new targeted therapies will undoubtedly provide new opportunities but whether or not this approach to therapy will lead to better results must still be determined.