Recent advances in basic research have greatly increased our understanding of the biologic events involved in the pathogenesis and progression of lung cancer. A multitude of genetic aberrations have been detected in both small-cell and non-small-cell lung cancer, many of which affect the function of known oncogenes and tumor-suppressor genes, which may serve as molecular targets for interventional trials. Recently identified abnormalities in oncogene expression and signal transduction pathways in premalignant lesions will be useful in devising future early diagnosis and chemoprevention studies. Numerous growth factor pathways control the proliferation and invasiveness of lung cancer cells and offer relatively tumor-specific targets for novel therapeutic approaches. Recent studies have defined several drug resistant mechanisms in lung cancer and have suggested methods for preventing and reversing treatment resistance. Insight into the biology of lung cancer will allow the improvement of current approaches to the prevention, diagnosis, and treatment of this devastating disease.