Next generation sequencing (NGS) has been widely used in identifying the most important driver genes to lung carcinogenesis. Compared to the traditional sequencing approaches such as Sanger sequencing, NGS has several distinct advantages including the capacity to fully sequence almost all of the genes in the whole genome, whole exome or whole transcriptome, and the ability to simultaneously detect all types of genetic variants such as base substitutions (mutations), insertions, deletions, copy number variants, structural variants, gene fusions, etc. In the past few years, several comprehensive NGS studies on three major types of lung cancer (lung adenocarcinoma, squamous cell lung cancer, and small-cell lung cancer) have been successfully conducted which both confirmed the significance of the previously identified lung cancer driver genes and revealed the ‘novel’ significant driver genes that were not well known in the lung cancer context before. Functional somatic genetic alterations in these genes exist in the majority of the lung cancer samples studied and altered the critical pathways whose aberrations have a direct impact on lung cancer development. It is anticipated that the expanding list of lung cancer driver genes will provide unprecedented opportunities to identify the best targets for lung cancer prevention and treatment.