The role of neoadjuvant chemotherapy in muscle-invasive bladder cancer has been clarified by recent randomized studies and meta-analyses, which all showed that cisplatin-based, combination chemotherapy offers a significant survival advantage. Preoperative chemotherapy results in downstaging in a significant percentage of patients, which is an independent factor of favorable prognosis. Nevertheless, the optimal sequence of perioperative chemotherapy remains undefined. The authors examine the results of large Phase II and randomized studies as well as the role of neoadjuvant chemotherapy in the context of bladder preservation strategies. Finally, issues of improving therapeutic efficacy and directing clinical research are discussed.