Successful integration of chemotherapy into the management of patients with invasive bladder tumors is critical to improve survival. With currently available treatment programs, only a modest improvement in survival can be anticipated. Thus, the routine use of chemotherapy for all patients with invasive bladder cancers cannot be recommended outside of the protocol setting. Research must focus on improving the proportion of patients who achieve complete remissions to therapy, because only complete responders have the opportunity to enjoy long-term survival. Effective salvage regimens need to be developed, along with a better understanding of the mechanisms of resistance to treatment. Equally important will be the ability to define which cases are destined to metastasize, for whom chemotherapy will be essential, as well as those who are not destined to develop metastatic disease, for whom chemotherapy is unnecessary. The choice of a neoadjuvant versus an adjuvant approach remains controversial. The ability to determine response in vivo, as well as the potential for bladder preservation, remains the primary benefit of neoadjuvant therapy. However, chemotherapy alone cannot replace definitive therapy for most patients, because the complete response proportions to chemotherapy alone remain under 30%. In other cases, postoperative adjuvant therapy may represent a better strategy, with the need for treatment based on pathologic as opposed to clinical grounds. Patients with nodal involvement at the time of surgery would be an appropriate group for whom therapy should be routinely recommended. It must be emphasized, however, that neither the neoadjuvant nor adjuvant approaches have been shown to definitively improve survival. This can only be demonstrated through randomized trials.