Gemcitabine has become one of the key drugs in the treatment of patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The overall response rate for single-agent gemcitabine is 25% with a complete response rate of 9% and toxicity is mild-to-modest. The overall response rate for gemcitabine combined with cisplatin (GC) in Phase II studies is 47% with a complete response rate of 18% and a median survival ranging from 12.5 to 14.3 months. A randomized Phase III study comparing GC and methotrexate, vinblastine, adriamycin and cisplatin (MVAC) has demonstrated similar efficacy with respect to response, time-to-progression and overall survival, whereas GC is associated with less toxicity than MVAC. Thus, GC is now considered a standard of care for patients with locally advanced and metastatic urothelial cancer. Other promising combinations include gemcitabine together with one of the taxanes with or without cisplatin.