Considerable debate exists concerning the combined use of systemic chemotherapy and radical surgery for muscle-invasive bladder cancer. While there is evidence for a survival benefit after neoadjuvant chemotherapy, the benefit is modest and the potential toxicity and delay of time to surgery prior to cystectomy appears to be deterring many surgeons from its administration. The evidence for adjuvant chemotherapy, on the other hand, is less compelling and substantial. Furthermore, the role of adjuvant compared to salvage chemotherapy requires further investigation. Similarly, research continues on identifying molecular and clinical markers to best stratify patients for optimal perioperative therapy. In this article, the evidence for radical cystectomy and chemotherapy, given either in a neoadjuvant or adjuvant setting, will be reviewed.