Treatment of progressive non-small cell lung cancer (NSCLC) has advanced remarkably, due in part to the development of targeted therapies. Several gene alterations, including EGFR, ALK, ROS1, and BRAF, play important roles in carcinogenesis. Therefore, many targeted agents focusing these gene alterations have been developed and proving their therapeutic efficacies in many clinical trials. Now we should test these gene mutations and should apply treatments individually and properly to ensure the maximal survival benefit of each patient. In this review, we summarize the target genes and respective therapeutic agents in NSCLC. (Korean J Med 2020;95:78-88)