The treatment of bladder cancer has evolved over time to encompass not only the 
traditional modalities of chemotherapy and surgery, but has been particularly 
impacted by the use of immunotherapy. The first immunotherapy was the live, 
attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the 
standard of care non-muscle-invasive bladder cancer since 1990. Modern 
immunotherapy has focused on inhibitors of checkpoint proteins, which are 
molecules that impede immune function, thereby allowing tumor cells to grow and 
proliferate unregulated. Several checkpoint targets (programmed death ligand-1 
[PD-L1] programmed cell death protien-1 [PD-1], and cytotoxic T-lymphocyte 
associated protein 4 [CTLA4]) have received the most attention in the treatment 
of bladder cancer, and have inhibitor agents either approved or in late-stage 
development. This review describes the most recent data on agents that inhibit 
PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B 
cells and macrophages. Atezolizumab is the only member of this class currently 
approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, 
durvalumab, and avelumab all have positive results for this indication, and 
approvals are anticipated in the near future. The checkpoint inhibitors offer an 
effective alternative for patients for whom previously there were few options 
for durable responses, including those who are ineligible for cisplatin-based 
regimens or who are at risk of significant toxicity. Research is ongoing to 
further categorize responses, define ideal patient populations, and investigate 
combinations of checkpoint inhibitors to address multiple pathways in immune 
system functioning.