Nivolumab is a fully human monoclonal antibody blocking PD-1 with demonstrated effectiveness against metastatic urothelial carcinoma. In this review, we describe the pharmacological properties of nivolumab and the treatment of metastatic urothelial carcinoma with this checkpoint inhibitor after the failure of first-line platinum-based chemotherapy. Cancer immunotherapy by checkpoint inhibition offers potential to prolong patient survival with well manageable toxicity although serious immune-related adverse events may occur. The overall response rate to nivolumab after first-line chemotherapy is about 20%. Patients unfit for cisplatin may benefit from first-line cancer immunotherapy. It remains unclear which patient will respond and PD-1/PD-L1 expression alone is not a sufficiently reliable predictive biomarker.