Immune checkpoint inhibitors for urothelial carcinoma in the relapsed/refractory setting have already been approved and are superseding standard chemotherapy. Now, there are exciting late-phase clinical trials investigating their use in the frontline setting. Speaking from the 2018 Genitourinary Cancers Symposium, held in San Francisco, CA, Thomas Powles, MD, of Barts Cancer Institute, London, UK, discusses whether checkpoint inhibitors could replace platinum-based chemotherapy as the new standard of care for urothelial cancer in all settings. Prof. Powles speculates on their use, either in combination with chemotherapy or other immunotherapeutics. He also discusses the further questions that need to be answered, including the selection of patients who will respond to this treatment.