Patients with localised but muscle-invasive transitional-cell carcinoma (TCC) of the bladder are at high risk of relapse and death from metastatic disease after local treatment by cystectomy, radiation, or both. Despite improvements in treatment, patients with metastatic TCC have a median survival of about a year. TCC is quite sensitive to chemotherapy, and patients are able to tolerate newer regimens such as gemcitabine plus cisplatin better than older regimens such as methotrexate, vinblastine, doxorubicin, and cisplatin. However, the role of chemotherapy in the management of locally advanced muscle-invasive TCC remains uncertain. Most trials of neoadjuvant or adjuvant chemotherapy have shown no significant improvement in survival, but many of these studies had suboptimum design, evaluated chemotherapy that was less effective than regimens in current use, and had sample sizes that were too small for important changes in survival to be detected or ruled out. Recent trials show trends in the direction of improved survival when optimum chemotherapy is used. Large trials that recruit more than 1000 patients are required to assess the effectiveness of adjunctive chemotherapy, and a large intergroup trial is in progress. Other trials should address the role of molecular markers in selecting patients for chemotherapy. Whenever possible, chemotherapy for locally advanced muscle-invasive TCC should be given in the context of a well-designed clinical trial.