Locally advanced bladder cancer comprising tumor stages pT3a, pT3b, pT4a of the 1997 TNM system and/or involvement of regional lymph nodes can be cured by radical cystectomy. However, at least 50% of patients experience systemic progression within 5 years after surgery. In order to improve the fate of these patients, the administration of additional therapy has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy, as well as combined radiochemotherapy. Results from more than a dozen randomized Phase III trials on adjunctive chemotherapy, which include cystectomy as definite treatment have been reported. Whether neoadjuvant or adjuvant systemic chemotherapy is the superior form of adjunctive therapy for locally advanced bladder cancer continues to be a matter of dispute.