Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidenceand mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemicchemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacyand overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumventthe problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumorscarry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence,the development of targeted agents against molecular subgroups harboring critical mutations is an attractiveapproach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemictherapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicityto normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the drivermutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance facedi n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.