Until the mid-twentieth century, opposition to tobacco use was based primarily on moral and social issues rather than specific health effects or strategies to control the problem. Since then, a comprehensive approach has been developed to counter the activities of the tobacco industry. National and international agencies work to protect non-smokers from tobacco smoke, decrease consumption by increasing the price of tobacco products through excise taxes, promote cessation, educate the public about the dangers of tobacco use, prohibit sales to minors, enforce bans on advertising, promotion, and sponsorship, and change social norms about tobacco use. Although this chapter cites mostly examples from the United States, the “Best Practices” for comprehensive tobacco control are now embedded in the WHO Framework Convention on Tobacco Control and the WHO Empower Initiative. These interventions were developed incrementally over decades and continue to be refined and tailored for effectiveness at the national and international level.