Although the incidence of bladder cancer has increased in recent years, survival has also improved. Chemotherapy has made a substantial impact on this disease and now is used in patients with advanced or metastatic disease as well as in select patients with high-risk muscle invasive disease. While cisplatin remains the most active single antineoplastic agent, several other agents including methotrexate, vinblastine, and Adriamycin (doxorubicin) have important activity. More recently, paclitaxel and gemcitabine have shown promising activity in bladder cancer. Multidrug combination therapy has provided more frequent and durable responses than single agent therapy. Regimens containing cisplatin and methotrexate have been shown to be most effective in the treatment of advanced disease. Adjuvant chemotherapy regimes typically have included cisplatin or cisplatin and methotrexate combinations. However, studies have been limited and further prospective trials are required to determine the role of adjuvant chemotherapy. Multiple studies have investigated neoadjuvant chemotherapy with cisplatin and methotrexate combinations or anthracycline-based regimens, but study results are mixed. Further trials will be required to define the role of neoadjuvant chemotherapy in bladder cancer.