Immunotherapies are now considered as a pillar of non-small-cell lung cancer treatment. The main targets of immune-checkpoint inhibitors (ICI) are programmed cell death 1/programmed cell death ligand 1 and cytotoxic T-lymphocyte antigen 4, aiming at restoring antitumor immunity. Despite durable responses observed in some patients, all patients do not benefit from the treatment and almost all responders ultimately relapse after some time. In this review, we discuss the biomarkers that could be used to predict response to ICI, the current indications of ICI in non-small-cell lung cancer, the mechanisms inducing tumor-cell intrinsic or extrinsic resistance to ICI and finally, the potential treatment response monitoring.