Lung cancer is the leading cause of cancer death in the United States and is responsible for 20,000 more deaths yearly in US women than breast cancer. Cigarette smoking is the major cause of lung cancer, and unfortunately, approximately 22 million US women smoke. Mounting evidence suggests that there are significant differences in lung cancer between the sexes. There is a difference in the histologic distribution of lung cancer, with glandular differentiation being more common in women. Genetic variation may account for differences in susceptibility, and hormonal and biologic factors may play a role in carcinogenesis. Lung cancer patients have few therapeutic options. A more thorough understanding of the heterogeneity of lung cancer across populations may lead to innovations in treatment and prevention strategies.