Accounting for 14,000 deaths in the USA last year, research informs us that advanced bladder cancer is a lethal disease with a median survival that has remained a little over 1 year for the past two decades. For the majority of patients with metastatic disease, chemotherapy with cisplatin-based combinations is the standard first-line treatment. Although initial response rates are high, disease progression is common, creating a growing number of patients in need of effective second-line chemotherapy. For this population, no standard of care currently exists. Salvage chemotherapy is associated with low response rates and studies exploring potential clinical benefit over supportive care alone are limited to nonrandomized Phase II trials. Vinflunine, a novel anti-mitotic drug from the Vinca alkaloid class, is the first and only agent that has been compared with supportive care in the second-line setting. In Europe, vinflunine is approved as a treatment option for patients with advanced urothelial cancer who have failed a prior platinum-containing regimen. To date, in the USA, there is no FDA-approved second-line chemotherapy for patients with metastatic bladder cancer and treatment continues to emphasize patient enrollment into a clinical trial.