Lung cancer is the leading cause of cancer death in US women and is responsible for as many deaths as breast cancer and all gynecological cancers combined. Most lung cancer is caused by cigarette smoke. Despite all that is known about the devastating effects of cigarettes, one quarter of women in the United States continue to smoke. Women are targeted in tobacco advertising, and teenage girls are often drawn to cigarette smoking under a variety of social pressures. Following the increase in smoking, the death rate from lung cancer in US women rose 600% from 1930 to 1997. Women may be more susceptible than men to the carcinogenic properties of cigarette smoke. In addition, differences in the biology of lung cancer exist between the 2 sexes with higher levels of DNA adduct formation, increased CYP1A1 expression, decreased DNA repair capacity, and increased incidence of K-ras gene mutations in women. The novel estrogen receptor beta has also been detected in lung tumors and suggests that estrogen signaling may have a biological role in tumorigenesis. Given these differences and given the enormous toll this disease has on US women, undertaking sex-specific research in lung cancer is crucial. Finally, disseminating information about this epidemic may prevent a similar epidemic in other parts of the world where women are just now becoming addicted to tobacco.