Immune checkpoint inhibitors have revolutionized the field of oncology, providing a novel mechanism for anticancer therapy. Programmed death 1-targeting antibodies pembrolizumab and nivolumab and programmed death ligand 1 (PD-L1)-targeting antibodies atezolizumab, durvalumab, and avelumab have been approved for use in advanced urothelial cancer in the post-platinum setting or in the upfront setting in platinum-ineligible patients. While this represents a significant step forward in management of urothelial cancers, most patients do not have an objective response to these therapies. PD-L1 expression is not a consistently predictive biomarker, but is recommended for checkpoint utilization in select circumstances. We report here a summary of known data and the differences between these agents, as well as future avenues to explore with immuno-oncologic agents in urothelial cancer. Much work is ongoing to better understand resistance mechanisms, to maximize efficacy with combination strategies, to find improved predictive biomarkers, to assess curative-intent strategies, and to better manage toxicity with these agents.