The problems associated with the use of alcohol, tobacco, and other drugs (ATOD) extract a significant health, social, and economic toll on American society. While the field of substance abuse prevention has made great strides during the past decade, two major challenges remain. First, the field has been disorganized and fragmented with respect to its research and prevention practices; that is, there are often separate ATOD prevention "specialists." Second, both the prevention researchers who test the efficacy of specific prevention strategies and the practitioners who implement prevention efforts often lack an overall perspective to guide strategy selection. To address these limitations, we present an ATOD causal model that seeks to identify those variables (Domains) that are theoretically salient and empirically connected across alcohol, tobacco, and illicit drugs. For the researcher, the model demonstrates important commonalities, as well as gaps, in the literature. For the practitioner, the model is a means to recognize both the complexity of the community system that produces ATOD problems and the multiple intervention points that are possible within this system. Researchers and practitioners are thus challenged to work synergistically to find effective and cost-effective approaches to change or reduce ATOD use and associated problems.