The outcomes for patients with previously treated advanced stage non-small lung cancer (NSCLC) are very poor, with a modest benefit from chemotherapy over best supportive care. Immunotherapy offers a novel approach for the treatment of these patients, with two anti-programmed death 1 (PD-1) checkpoint inhibitors, nivolumab and pembrolizumab, recently approved by the FDA based on large randomized clinical trials showing increased overall survival compared with standard second-line docetaxel. Although only a subset of patients benefit from these drugs, the treatment is usually well tolerated and the responses are often durable, with an unprecedented number of survivors 3 years after starting the therapy. The next steps should be the identification of reliable predictors for benefit from immunotherapy with checkpoint inhibitors and the pursuit of welldesigned combination therapies. In this article, we review the rationale for the use of checkpoint inhibitors in NSCLC, the data from phase I and randomized clinical trials, and future directions.