The incidence of locally advanced bladder cancer is estimated at 5 new cases per 100,000 of the population annually in North America and most European countries. Radical cystectomy for muscle-invasive organ-confined tumors and locally advanced disease, which is defined as extravesical tumor growth or involvement of regional lymph nodes, is the preferred treatment in Japan, the United States, and in some countries of Europe. The clinical outcome of radical cystectomy has improved remarkably over the past 20 years as a result of advances in operative technique and perioperative care. Nevertheless, at least 50% of patients with invasive bladder cancer are expected to develop progressive disease within the first 2 years when treated with radical cystectomy alone. In order to improve the fate of muscle-invasive and locally advanced disease, the administration of additional therapy to definite treatment has been studied in various forms, such as neoadjuvant and adjuvant systemic chemotherapy as well as combined radio-chemotherapy. Prolonged progression-free survival for patients suffering from locally advanced bladder cancer by administration of adjuvant systemic chemotherapy has been suggested by three randomized studies, published by Skinner, Freiha and Stöckle since 1991. These studies demonstrated a disease-free survival benefit of 17-50% within the first 3-5 years when applying adjuvant systemic chemotherapy after radical cystectomy. Patients who most likely benefit from adjuvant chemotherapy are those with limited node-positive disease, extravesical tumor, and direct invasion into adjacent viscera, such as prostate, uterus, or vagina. This review will summarize past, current, and future aspects of systemic adjuvant chemotherapy for transitional cell carcinoma of the bladder.