Lung cancer remains the number one cause of cancer death in the United States. Even with advances in understanding of tumor histology and mutation status, outcomes remain poor with classic cytotoxic therapies. The development of immune checkpoint inhibitors, designed to optimize a host’s own immune response against cancer cells, has led to a new era in the treatment of non–small cell lung cancer (NSCLC). Improved survival in trials have led to rapid US Food and Drug Administration approval for these agents in the advanced-stage NSCLC setting. Many studies are looking at these agents across a variety of patient populations, treatment settings, and in combination with other agents. Because of their unique mechanism of action, tumor response kinetics and patient adverse effect profiles vary greatly from cytotoxic chemotherapy and demand further study. Understanding the optimal use of these agents continues to be elucidated as they shift the NSCLC treatment paradigm.