Although cystectomy remains the standard for treatment of muscle-invasive bladder cancer in the United States, there exist potentially curative alternatives for a selected subset of these patients in organ preservation using concurrent chemotherapy with radiation following an aggressive transurethral resection of the tumor. Chemotherapy and radiotherapy in combination, with salvage cystectomy for invasive recurrence, have produced 10-year disease-specific survival rates of 60% to 65% with overall survival similar to that of cystectomy in selected patients. Fine-tuning of the chemoradiotherapy sequencing, timing, and fractionation has been reported in both single-center and cooperative group publications from North America and Europe.