Patients with SCLC (Small cell lung cancer) have been treated differently from those with NSCLC (New-small cell lung cancer) as a different disease. Recently, even patients with NSCLC are treated differently according to histological subtypes. This change is associated with the development of new drugs, particularly molecular-targeted drugs. Because Bevacizumab can cause serious adverse effects, patients with squamous cell carcinoma histology and a history of hemoptysis are contraindicated for this drug. Pemetrexed has been approved with an anti-mesothelioma drug and was confirmed to be effective for NSCLC. However, its efficacy was not equally proved among the histological subtypes; only adenocarcinoma patients showed shorter progression-free and prolonged survival periods. Regarding tyrosine kinase inhibitors, the targeted gene alterations occur specifically in adenocarcinoma. Based on these findings, the current therapeutic strategy for NSCLC is based on the histological subtype and mutational status of EGFR and ALK. In this article, transition of the therapeutic strategy for NSCLC, characteristics of targeted gene alterations and efficacies of the targeted therapy are reviewed.