Patients with muscle-invasive transitional cell carcinoma of the bladder are at high risk of systemic relapse following primary therapy. Several randomized trials of neoadjuvant and adjuvant chemotherapy suggest that chemotherapy administered before or after primary therapy may improve the disease-free survival of patients with invasive bladder cancer. The effects of neoadjuvant and adjuvant chemotherapy on long-term survival remain controversial. Potential differences in the long-term outcome of patients treated with neoadjuvant and adjuvant chemotherapy are not known. The only randomized trial comparing these 2 approaches showed no difference in survival with short median follow-up. Treatment recommendations for an individual patient require consideration of the relative advantages and disadvantages of chemotherapy administered before or after primary therapy. Recommendations regarding the optimal treatment of patients with invasive bladder cancer await the results of ongoing randomized trials. Because the use of adjuvant and neoadjuvant chemotherapy in patients with invasive bladder cancer represents a promising but unproven approach, physicians should encourage patients with invasive bladder cancer to enroll in clinical trials.