At present, it is clear that chemotherapy can contribute to improved outcome for some patients with locally advanced bladder cancer. For patients in clinical stage T3b, the incidence of pathological node involvement is no high that little is lost by giving up precise staging, and neoadjuvant therapy is probably the preferred approach. This is based on improved tolerance for chemotherapy, improved resectability rates, and the desirability of addressing metastatic disease at the earliest opportunity. Although more experience is needed, at present the surgical complication rate for cystectomy after chemotherapy does not appear to be significantly higher than immediate surgery. For patients thought to have T2/3a lesions according to clinical evaluation who are subsequently found to have stage pT3b at operation, the evidence for benefit from chemotherapy is not yet conclusive, and we consider use of adjuvant therapy in this setting to be investigational. It is hoped that refinement of clinical markers and continued improvement in combination regimens will allow more effective therapy to be targeted more selectively in the future.