The microtubule inhibitor vinflunine is currently the only cytotoxic drug approved in Europe for the treatment of patients with metastatic transitional cell carcinoma who failed first-line platinum-based chemotherapy. Indeed, the only Phase III trial ever conducted in this setting demonstrated a benefit in progression-free and overall survival for patients receiving vinflunine plus best supportive care compared with best supportive care alone. Recent data from European studies performed in real life confirmed the efficacy of the drug, even in patient populations exhibiting adverse prognostic factors. Side effects were manageable, provided gastrointestinal prophylaxis is performed. The potential role of vinflunine in first-line treatment as maintenance therapy or as a partner in combination chemotherapy for patients unfit for cisplatin is currently being investigated.