There is an increasing momentum to integrate prevention into mainstream health care. Three decades of research on tobacco dependence can provide insights into the conceptual, clinical, economic, and service delivery challenges to such an integration. Biological sciences, cognitive-behavioral, clinical treatment outcome, and public health arenas are selectively reviewed. The key conceptual issues are explored relevant to the optimal delivery of quality smoking cessation treatments for the general population of adult smokers at reasonable cost. A comprehensive model for adult smoking cessation treatment is developed. The model consists of an overarching public health approach, focusing on enhancing motivational level from low motivation to quit to high motivation. A common outcome metric of overall impact is proposed to facilitate comparisons between clinical and public health interventions. Smokers are then assessed and triaged into one of three treatment steps of minimal, moderate, and maximal intensity and cost. Smoker individual differences at both the population and individual level are also taken into account as part of a tailoring or matching strategy within and across the stepped interventions. Smoker profiles include sociocultural, nicotine dependence, and comorbidity factors. The result is a hybrid stepped-care matching model. The model serves to illustrate some of the needs and challenges facing future tobacco dependence research and practice. Comparisons are made between tobacco control and other preventive medicine practices in terms of cost per quality adjusted life-year saved. The barriers and opportunities under managed care are explored. The conceptual principles identified here could be used as a guidepost for integrating other preventive medicine programs into the evolving managed health care system.