Bladder cancer is a paradigm of malignancy, representing the spectrum from localized to metastatic disease, and manifesting varied histologic types, including transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. Preclinical and clinical data suggest that a common stem cell of origin gives rise to the different histologic types and that these patterns are of clonal origin. Localized bladder cancer is managed optimally by transurethral resection, with or without adjuvant intravesical chemotherapy. Invasive cancer or relapsed superficial disease may require more radical surgery or radical radiotherapy. In recent years, the evolution of techniques of continent urinary diversion or of bladder replacement has revolutionized the management of invasive disease. However, the 5-year survival for invasive bladder cancer is still approximately 50%, and innovative strategies have been developed, combining definitive local treatment and systemic chemotherapy, in an attempt to improve survival. For patients with metastatic disease, the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (the MVAC regimen) has achieved response rates as high as 70% but with a median survival of only 12 months. Until cure rates are improved, one of the hallmarks of effective management of metastatic disease will remain the provision of thorough and well-structured palliative treatment programs. Recently, the introduction of new agents (such as paclitaxel, gallium, ifosfamide, and gemcitabine) has led to promising response rates, and further clinical trials of these agents alone and in combination are in progress. In addition, an improved understanding of the mechanisms of resistance to treatment, including the implications of the expression of p-glycoprotein, p53 proteins, and other biochemical predictors of outcome, and of strategies to overcome such resistance, may lead to more effective management of advanced disease. Furthermore, real progress will be made only through the application of well-designed clinical trials to test the efficacy and toxicity of the new strategies of treatment.