The optimal management of invasive bladder cancer remains controversial. Combination chemotherapy regimens have been increasingly advocated in association with definitive local therapy in an attempt at eradicating micrometastases and reducing the risk of recurrence. Chemotherapy used after radical cystectomy is referred to as "adjuvant" therapy. The term adjuvant is occasionally used for chemotherapy following an aggressive transurethral resection (TUR). Decisions concerning individual patients must be made after careful examination of the histologic specimen and cognizance of the known relapse rates per pathologic stage. No randomized trial has reported results on patients with pT 2 and pT 3a tumors. Studies have not clearly proven any advantage for adjuvant therapy based on muscle infiltration alone (pT 2, pT 3a). For patients with minimal extravesical extension (pT 3b), additional therapy may be useful. For patients with nodal metastases (pN+) and direct extension into the adjacent viscera (pT 4), the data suggest a trend toward improved survival. These patients may benefit from adjuvant chemotherapy. The difficulties of clinical trials following cystectomy, conducted in an elderly patient population, done over a long period, with changing standards of effective chemotherapeutic regimens are described. Adjuvant therapy following cystectomy or an aggressive TUR remains investigational and its benefit has not yet been proven. Patients should be entered into well-designed and carefully conducted clinical trials to evaluate the role of chemotherapy in invasive bladder cancer.