Chemotherapy and targeted therapy have significantly improved the progression of non-small cell lung cancer (NSCLC), but patients are inevitably suffering from drug resistance and relapse. With this background, the immunotherapy brings a turnaround for a subset of cancer patients. Over two decades, with the development of immunotherapy, immune checkpoint inhibitors (ICIs) have made a breakthrough in NSCLC patients. ICIs targeting the programmed death 1 receptor (PD-1), programmed cell death receptor ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) showed significantly antitumor efficacy, produced durable clinical responses, and prolonged survival by regulating T cell-mediated immunologic responses in patients with advanced/refractory and metastatic NSCLC in clinical trials. This review aims to summarize the recent advances and challenges of ICIs including nivolumab, pembrolizumab, PF-06801591, MEDI0680, atezolizumab, durvalumab, ipilimumab, tremelimumab, and other new PD-1/PD-L1 and CTLA-4 inhibitors in immunotherapy of NSCLC. We hope to provide a better understanding of the mechanisms, clinical research progress and future research directions of NSCLC immunotherapy.Copyright © 2020 Elsevier B.V. All rights reserved.