OBJECTIVE: The aim of the present paper is to review findings from the most relevant studies and evaluate the potential of new drugs in treatment of metastatic urothelial cancer. METHODS: Studies were identified by searching MEDLINE and Pubmed databases up to 2009 using both medical subject heading (Mesh) and a free text strategy with the name of known individual chemotherapeutic drug and the following key words: 'muscle-invasive bladder cancer', 'urothelial/transitional carcinoma', 'chemotherapeutics drugs and agents'. At the end of our research in literature we selected 63 articles and we have considered only studies in which almost 30 patients were enrolled. RESULTS: Radical cystectomy with pelvic lymph node dissection is the gold standard of treatment for clinically localized muscle-invasive bladder cancer. While more extensive lymph node dissection may have both prognostic and therapeutic significance, effective systemic therapies that eliminate micrometastases may improve outcome. Perioperative chemotherapy can be administered before (neoadjuvant) or after (adjuvant) cystectomy to eradicate subclinical disease and to improve survival. CONCLUSION: The challenge remains as to how to integrate all of the relevant knowledge and data in a systematic manner so that researchers can gain the knowledge needed to devise the best therapeutic and diagnostic strategies. Future improvements in the treatment of advanced bladder cancer will rely not only on the optimization of currently available cytotoxic agents but also on the biologic profile of individual patient tumors and the appropriate therapies that target molecular aberrations unique to this malignancy.