Urothelial carcinoma of the urinary bladder is the second most common genitourinary malignancy. Based on the results of a large randomized study comparing MVAC with gemcitabine plus cisplatin, the latter regimen became a treatment standard based on improved tolerability. While the tolerability of chemotherapy for patients with advanced urothelial carcinoma has improved, there have been no significant improvements in efficacy since the advent of MVAC in the 1980's and novel approaches are clearly needed.