Lung cancers are a leading cause of mortality worldwide, and most of these neoplasms are directly attributable to tobacco abuse. Recent studies have begun to elucidate molecular mechanisms of multistep aerodigestive tract carcinogenesis, revealing novel targets for intervention in lung cancers and their precursor lesions. This review summarizes the molecular biology of lung cancers in relation to the prognosis and treatment of patients with these neoplasms.