We review the molecular pathogenesis of lung cancer including alterations in dominant oncogenes, recessive oncogenes/tumor suppressor genes, alterations in growth regulatory signaling pathways, abnormalities in other pathways, such as apoptosis, autocrine and paracrine growth stimulatory loops, angiogenesis, and host immune responses, other mechanisms of genetic changes, such as microsatellite and methylation alterations, and the potential for inherited predisposition to lung cancer. These changes are related to multistage carcinogenesis involving preneoplastic lesions, and lung development and differentiation. The translational applications of these findings for developing new ways of early detection, prevention, treatment, and prognosis of lung cancer are discussed.