Over the past century, lung cancer has gone from an obscure disease to the leading cause of cancer death worldwide. Initially an epidemic disease among men in industrialized nations, lung cancer now has become the leading cancer killer in both sexes in the United States and an increasingly common disease of both sexes in developing countries. Lung cancer incidence largely mirrors smoking prevalence, with a latency period of several decades. Other important risk factors for the development of lung cancer include environmental exposure to tobacco smoke, radon, occupational carcinogens, and pre-existing nonmalignant lung disease. Studies in molecular biology have elucidated the role that genetic factors play in modifying an individual's risk for lung cancer. Although chemopreventive agents may be developed to prevent lung cancer, prevention of smoking initiation and promotion of smoking cessation are currently the best weapons to fight lung cancer. No other malignancy has been shown to have such a strong epidemiologic relation between a preventable behavior and incidence of disease. Despite this knowledge, more than 20% of all Americans smoke, and tobacco use is exploding in developing countries. Based on current and projected smoking patterns, it is anticipated that lung cancer will remain the leading cause of cancer death in the world for decades to come.