This article, based on B. McCrady, D. Haaga, and J. Lebow (2006), provides guidance for the treatment of substance use disorders by identifying empirically based principles that underpin effective treatment systems and effective treatments. To promote the flexible application of empirically based principles to individual clients, the authors (a) integrate therapeutic, participant, and relationship factors (drawn from reviews by B.S. McCrady & P.E. Nathan, 2006; D.A.F. Haaga, S.M. Hall, & A. Haas, 2006; and J. Lebow, J. Kelly, L.M. Knobloch-Fedders, & R. Moos, 2006) into a comprehensive description of treatment, (b) integrate common and specific principles of changes into articulated descriptions of treatment, and (c) identify directions for research to improve the sensitivity and specificity of treatment.