Just as the American Stop Smoking Intervention Study for Cancer Prevention (ASSIST) was a major shift in the National Cancer Institute's (NCI's) tobacco prevention and control research and dissemination efforts, this monograph is a significant departure from NCI's previous tobacco control monographs. For many, the ASSIST project represented a logical progression of NCI's phased-research approach to reducing tobacco use. For others, it represented a controversial and overly ambitious leap in a new direction. Similarly, this monograph departs from the traditional quantitative evidence review format to emphasize instead the practical, hands-on experience of program implementation. Traditional research investigators who defend the sanctity of the randomized clinical trial, many of whom were uncomfortable with ASSIST at its outset, will also be uncomfortable with the personal and anecdotal flavor of this monograph. Public health practitioners, on the other hand, as well as those investigators who have immersed themselves in the untidy world of implementation research, will appreciate the detailed historical accounts of the complexities, politics, and outright opposition encountered by the ASSIST team. The collective experiences described in this monograph provide a rich understanding of the gritty struggle against the powerful forces of the tobacco industry and its allies. For students in public health training programs, this work also provides a unique view of the world outside of academia, where commercial, political, and public health interests collide in a struggle to define the policies, norms, and practices that will affect the health of generations. Monograph 16 begins with the historical context of ASSIST and the scientific base that informed the design of the project. The conceptual framework and the development of organizational infrastructures for implementation and evaluation are then described. The heart of this monograph is the in-depth descriptions of ASSIST's media advocacy and policy development interventions and the challenges posed by the tobacco industry. The monograph concludes by describing ASSIST's contributions to tobacco control and other behavioral health interventions and the significant challenges that remain.