Tobacco has a long history of use in the U.S., and its serious health effects have been well-documented during the past half century, U.S. efforts to control tobacco use and tobacco-related morbidity and mortality have been reasonably successful over the past 25 years, during which time there has been a 34 percent reduction in adult smoking. Nevertheless, tobacco use remains a significant public health problem in the U.S., with more than 430,000 tobacco-related deaths per year and over one-fourth of the population continuing to smoke. Many organizations are involved in tobacco use control activities, the most broadly focused of which is the National Cancer Institute (NCI). As an example of the type of program needed to address the problem of tobacco use on a national scale, the NCI's public health research plan and activities are described and its emphasis on a data-based decision matrix in its approach to tobacco and cancer control research and applications of research is discussed. Finally, future approaches to tobacco use control in the U.S. are suggested.