Muscle-invasive urothelial (transitional cell) carcinoma is a potentially lethal condition for which an attempt at curative surgery is required. Clinical staging does not allow for accurate determination of eventual pathologic status. Muscle-invasive urothelial carcinoma is a highly progressive disease, and initiation of definitive therapy within 3 months of diagnosis is worthwhile. Age is not a contraindication for aggressive surgical care, and surgical candidates should be evaluated in the context of overall medical comorbidity. In those patients who undergo surgery, clinical pathways may streamline care. Radical cystectomy remains the “gold standard” of therapy, providing 5-year survival rates of 75% to 80% in patients with organ-confined disease, yet organ-sparing procedures demonstrate clinical effectiveness as well. Cystectomy should be undertaken with the intent of performing complete pelvic lymph node dissection and attaining surgically negative margins. In younger female patients, the preservation of reproductive organs may be achieved in many cases. Prostate- and seminal vesicle–preserving cystectomy has been performed, yet the long-term safety and efficacy of such a procedure remains to be determined. Laparoscopic and robotic cystectomy procedures continue to be explored by several investigators. The role of “radical transurethral resection” in muscle-invasive disease is limited to a small cohort of patients, and, when it is performed, cystectomy may be required to consolidate therapy. Postoperative follow-up after cystectomy should occur over short intervals during the first 2 years and can be extended, but not discontinued, beyond that time. Currently, no tumor markers have been prospectively validated to help guide clinical decision making, and prospective trials incorporating marker data should be encouraged.