Increasingly, drug use prevention programs and research are being considered in the environmental contexts in which they occur. One context that is rarely considered is the political context. This article examines the reciprocal effects of policy and prevention programs from four perspectives representing different contexts, beginning with political science, and followed by social work and public health administration, psychology, and education. Four specific issues are considered. First is how current national policies on drug use shape our nation's prevention efforts, from a political science perspective. Second is how effective prevention programs can affect and shape policy change. This issue is considered from a social and public health administration perspective. Third is how policy change can act as an intervention to prevent drug use, from the perspective of psychology. The fourth issue is how dissemination of prevention programs and policies can impact drug use prevention. This question considers an educational perspective. The perspectives are integrated into a general conceptual model to improve our understanding of how drug use prevention occurs in a national political context. Finally, examples are given of how this model might inform the other perspectives represented in this special issue on transdisciplinary drug abuse prevention research.