Although the prevalence of lung cancer in men has been decreasing, it has been increasing in women. Without a doubt, lung cancer is a major health problem for women in the USA, not only owing to its high incidence rate but, more alarming, the high mortality rate. Lung cancer kills more women each year than breast, ovarian and uterine cancers combined. One of the most important risk factors for the development of lung cancer in both men and women is cigarette smoking. Unfortunately, the prevalence of smoking among women has increased significantly since 1980, which is a major concern as epidemiologic data suggest that women may be more susceptible to developing lung cancer than men. Many will argue, however, that after adjusting for tobacco exposure, some studies have failed to show that women are at a higher risk for developing lung cancer. Indeed, the increased risk of lung cancer in women remains controversial. There is, however, little controversy to the fact that the biology of lung cancer differs between the sexes. This paper summarizes the explanations for the sex differences in lung cancer, including differences in molecular abnormalities, growth factor receptors, hormonal influences, differences in cytochrome P-450 enzymes and DNA repair capacity, as well as variations in treatment outcomes.