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Purpose Successful immuno-oncology research over the past few decades has driven the widespread clinical application of immune checkpoint inhibition, the activation of the bodies’ immune system to combat malignant tumor cells, in the management of various cancers. The utilization of the checkpoint inhibition mechanism in the treatment of advanced non-small cell lung cancer (NSCLC) became the standard second-line therapy in 2015 with the FDA approval of Nivolumab and Pembrolizumab. Design This review provides a synopsis of the existing knowledge of the role of the immune system in the pathogenesis of malignant tumors and examines the mechanism of action of immune therapies, as well as discussing the data from the clinical studies responsible for the approval of immune checkpoint inhibition in the treatment of advanced NSCLC. Results Three recently-approved drugs: Nivolumab, Pembrolizumab and Atezolizumab, and Durvalumab, currently under FDA review, have shown favorable overall survival, overall response rate, duration of response and/or toxicity/safety profiles in a number of single agent and combination therapy clinical trials compared to standard of care platinum-based doublet chemotherapies for advanced NSCLC patients who have metastatic disease, have failed standard-of-care therapy, or are treatment-naive. Conclusion Current and future research will focus on novel immunotherapeutic agents and additional drug combination trials, as well as investigating tumor-specific biomarkers, including PD-L1 expression and other immune signatures, to predict which patients may best benefit from the new checkpoint inhibition drug regimens. In the near future, clinicians will have more choices of potential first line treatment regimens for NSCLC patients, and eventually targeted therapies and immunotherapy may prove more efficacious and safer than current platinum-based chemotherapy.