Immune checkpoint inhibition using targeted monoclonal antibodies is changing the treatment paradigm for lung cancer. Approval by the US Food and Drug Administration of two anti-programmed death 1 immune checkpoint inhibitors for second-line treatment of advanced or metastatic non-small-cell lung cancer (NSCLC) has led to increased use of these agents in the clinic. Ongoing clinical trials are evaluating the administration of immune checkpoint inhibitors alone or in combination with each other, and in combination with targeted therapy, radiation therapy, and chemotherapy regimens. Other trials are evaluating these monoclonal antibodies in small-cell lung cancer and across a variety of treatment regimens and disease stages in NSCLC. Ongoing translational work to identify relevant biomarkers will deepen our understanding of when and how to use immune checkpoint agents in our patients with lung cancer. We must continue to improve the cost-benefit ratios for efficacy, safety, and outcomes associated with the use of these medications. This is an exciting time in the field of lung cancer research as we work to understand how best to use this novel class of agents.