Tobacco use remains the nation's leading cause of preventable premature mortality. Lung cancer, one of the many cancers caused by tobacco use, is both the leading cause of cancer death in the United States and the leading cause of male cancer death globally. This special issue of Risk Analysis features the work of the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET), which finds that changes in Americans’ smoking behaviors that began in the mid 1950s averted nearly 800,000 U.S. lung cancer deaths in the period 1975–2000 alone. However, this figure represents only about 30% of the lung cancer deaths that could potentially have been averted during this period. Despite dramatic declines in smoking prevalence since the mid 1960s, tobacco use is still far too common; today about one in five American adults smokes cigarettes. The tobacco industry's role in promoting tobacco use is now well documented and, as noted by the President's Cancer Panel, “can no more be ignored in seeking solutions to the tobacco problem than mosquitoes can be ignored in seeking to eradicate malaria.” Recent developments, including the passage of legislation granting the Food and Drug Administration broad authority to regulate tobacco products, and the entry into force of the Framework Convention on Tobacco Control, an evidence-based treaty developed by the World Health Organization, hold great promise to more swiftly end the epidemic of lung cancer and other tobacco-caused diseases that exacts such a heavy toll in human suffering in the United States and around the world.