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. Between the extremes of superficial and advanced disease, muscle-invasive bladder cancers have traditionally been treated, with curative intent, by radical surgery or radiotherapy. However, newly published data suggest, for the first time, genuine survival benefits from peri-operative chemotherapy. This article reviews the evidence for cisplatin-based chemotherapy in advanced disease, assesses the potential benefits of newer cytotoxic drugs, discusses the latest evidence pertaining to peri-operative chemotherapy in muscle-invasive disease, and looks forward to potential new biological agents in the systemic therapy of bladder cancer.