Advancements in the understanding of tumor immunology in urothelial carcinoma 
(UC) have led to U.S Food and Drug Administration (FDA) approval of five novel 
anti-programmed cell death protein-1/ligand 1 (PD-1/L1) checkpoint inhibitors. 
In 2017, the anti-PD-L1 antibody atezolizumab and the anti-PD-1 antibody 
pembrolizumab gained approval for use in cisplatin-ineligible patients with 
locally advanced and metastatic UC. These approvals were based on single-arm 
trials, IMvigor210 (atezolizumab) and KEYNOTE-052 (pembrolizumab). Since then, 
additional checkpoint inhibitors, including avelumab, durvalumab, and nivolumab, 
have gained approval. Preliminary results suggest additional benefits with 
combinations of these agents in both first- and subsequent-line therapies, 
inferring a paradigm shift in the future treatment approach in advanced UC. 
Ongoing clinical trials will investigate how to utilize predictive biomarkers 
for optimal patient selection and to incorporate immunotherapy into earlier 
lines of multimodal treatment. In this comprehensive review, we summarize the 
evidence supporting the use of checkpoint inhibitors for patients with UC, and 
highlight ongoing clinical trials that are investigating novel combinations of 
immunotherapy in various disease settings.