Immune checkpoint inhibition will be the first treatment breakthrough in recurrent and metastatic urothelial carcinoma since the introduction of combination chemotherapy more than 30 years ago. Monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4, programmed death receptor 1, and programmed death receptor ligand 1 are furthest along in clinical development. Specific antibodies targeting either programmed death receptor 1 or programmed death receptor ligand 1 have demonstrated significant single-agent activity with impressive safety and tolerability for heavily pretreated patients in early-phase clinical trials. In our review, we discuss the rationale for immunotherapy in urothelial cancer, completed and ongoing studies with immune checkpoint therapy, the development of molecular subtypes of urothelial carcinoma with the potential impact of immunotherapy in these new groupings, and future directions of exploration with these agents in both early- and late-stage disease.