As emerging means of cancer treatment, immunotherapy is the fourth major therapeutic strategy after surgery, chemoradiotherapy, and targeted therapy, which benefits patients a lot. It has been more than 100 years for the medical community exploring how to harness the immune system to fight cancer. Since the advent of ipilimumab in 2011, the first checkpoint inhibitor, cancer immunotherapy represented by checkpoint inhibitors has exploded. Several programmed death protein-1 and programmed cell death ligand-1 inhibitors have successively been approved to treat advanced non-small cell lung cancer in the second-line setting or even the first-line setting. But checkpoint inhibitors therapy has only achieved limited benefit at the present stage. Exploring potential predictive biomarkers and mechanisms of resistance are in need of further consideration to optimize immunotherapy.