Purpose: Sound public health policy is based on relevant and timely information. A brief review of the history of youth tobacco control illustrates the central role of epidemiology to inform policy choices and evaluate their consequences. Methods: A narrative review was conducted. Results: Epidemiologic studies have shown that most smokers begin as adolescents or young adults and individuals who reach their mid-20s as nonsmokers are unlikely to ever become smokers. This key recognition made it clear that long-term tobacco control must prevent initiation of smoking among youth. Over time, tobacco use prevention interventions have evolved, increasing in reach and effectiveness as they moved from initially focusing on the individual to an approach that targets both populations and communities. Effective interventions for preventing youth smoking include raising tobacco prices, clean indoor air laws, and intensive mass media campaigns. Conclusions: Great strides have been made in youth tobacco control but 18% of high-school students continue to smoke. It is up to epidemiologists, fellow scientists, practitioners, and advocates to assure that strategies that are known to work are fully implemented and to continue to find more successful solutions that can further lower the incidence of youth smoking initiation and can address new tobacco products and changing contexts.