Muscle-infiltrating bladder cancer should be dealt with in a multimodality approach with collaboration between the urologist, medical oncologist and radiotherapist. Neo-adjuvant chemotherapy has not been proven to improve survival, but may be useful in programs of bladder preservation. Response to M-VAC neo-adjuvant chemotherapy is an important prognostic factor, but may represent patient selection factors. It is not known whether it is better to administer chemotherapy in the neo-adjuvant or in the adjuvant setting, that may spare some patients unnecessary chemotherapy. The international adjuvant chemotherapy trial coordinated by the EORTC (protocol 30994) will hopefully clarify some of the unanswered questions concerning whether or not adjuvant chemotherapy immediately following cystectomy improves survival.