With the emergence of five novel immune checkpoint inhibitors for the treatment of urothelial carcinoma, the key question now arising is how to identify the subgroups of patients who will benefit from this therapy. As discussed here by Thomas Powles, MD, of Barts Cancer Institute, London, UK, PD-L1 expression is the primary biomarker used. However, Prof. Powles points to a second-generation of biomarkers emerging, including RNA expression, tumor mutational burden (TMB) and TGF-?. This video was recorded at the 2018 Genitourinary Cancers Symposium, held in San Francisco, CA.