Many localised, superficial bladder cancers can be effectively controlled. However, disease which has spread to nodes outside the pelvis or to distant organs is generally incurable and systemic therapies, rather than surgery, are appropriate. Combination chemotherapy based around established cytotoxic drugs such as cisplatin has proven benefit in palliating symptoms and prolonging survival in responsive patients with advanced disease. Combination chemotherapies which include newer cytotoxic drugs such as gemcitabine provide the potential for equivalent efficacy with less toxicity than established regimens. This article reviews the evidence for cisplatin-based chemotherapy in advanced disease, assesses the potential benefits of newer cytotoxic drugs, discusses the latest developments in patient risk assessment and evidence pertaining to treatment of patients no candiates to cisplatin, and looks forward to potential new biological agents and combinations in the systemic therapy of bladder cancer. Copyright © 2005 Aran Ediciones, S. L.