Lung cancer is the most common cause of cancer death in the United States, killing more than 156,000 people every year. In the past two decades, significant progress has been made in understanding the molecular and cellular pathogenesis of lung cancer. Abnormalities of proto-oncogenes, genetic and epigenetic changes of tumor suppressor genes, the role of angiogenesis in the multistage development of lung cancer, as well as detection of molecular abnormalities in preinvasive respiratory lesions, have recently come into focus. Efforts are ongoing to translate these findings into new clinical strategies for risk assessment, chemoprevention, early diagnosis, treatment selection, and prognosis and to provide new targets and methods of treatment for lung cancer patients. All these strategies should aid in reducing the number of newly diagnosed lung cancer cases and in increasing the survival and quality of life of patients with lung cancer.