With this volume, the National Cancer Institute (NCI) presents the 17th monograph of the Tobacco Control Monograph series. This monograph documents the evaluation of a groundbreaking NCI program. The American Stop Smoking Intervention Study for Cancer Prevention, known as ASSIST, put into practice NCI's commitment to prevent and reduce tobacco use across all populations and age groups. ASSIST took evidenced-based interventions from controlled studies and implemented them in the larger community of 17 states. Its underlying rationale—that significant decreases in tobacco use could be realized only with interventions that changed the social environment such that smoking was non-normative—was a significant departure from previous tobacco control programs and in the vanguard of the “new” public health. Prior to ASSIST, few states addressed tobacco use at the population level. The ASSIST legacy remains today in the tobacco control professionals whose work continues to reduce the burden of disability and death caused by tobacco. ASSIST raised significant conceptual and practical challenges for its evaluation team. These challenges included context-dependent implementation and the diffusion of ASSIST and ASSIST-like interventions into non-ASSIST states. In addition, the evaluation did not begin until several years after ASSIST was implemented, and its budget was limited. What had been envisioned as a simple evaluation of a demonstration project became a complex evaluation effort that engaged a diverse group of scientists and practitioners and required numerous sources of data. The resulting evaluation successfully documented the effectiveness of ASSIST. It also validated the causal pathway described in NCI's 1991 Smoking and Tobacco Control Monograph 1: Strategies to Control Tobacco Use in the United States: A Blueprint for Public Health Action in the 1990's—that comprehensive interventions can change the social environment of tobacco use and subsequently result in decreased tobacco use. This monograph stands alone as a documentation of the ASSIST evaluation and describes the challenges met in evaluating a program that was influenced by numerous forces outside the program's control. However, this monograph may also be viewed as a companion to NCI Tobacco Control Monograph 16, which reviews the ASSIST program in detail. Together these two monographs provide a detailed history and evidence base that document the success of an NCI initiative that began with a series of research hypotheses, tested those hypotheses with community-based interventions, and ultimately fielded a demonstration program that fundamentally changed tobacco use prevention and control in the United States. This volume and several future volumes in the Tobacco Control Monograph Series have important implications for research, practice, and policy in tobacco control as well as in other areas of public health. Lessons learned from tobacco prevention and control can be applied to a variety of public health issues, including physical activity, diet and nutrition, overweight and obesity, and substance abuse. NCI is committed to disseminating this cross-cutting knowledge to the widest possible audience so that others can benefit from the experience of the tobacco prevention and control community. By so doing, NCI is increasing the evidence base for effective public health interventions and improving the translation of research to practice and policy.