Contemporary substance abuse treatment providers are now recognizing the growing diversity within American society. This recognition includes a growing appreciation of racial/ethnic diversity, although few models exist to aid in conceptualizing this diversity as related to substance abuse treatment. This situation prompts the need to better understand the influences of cultural variables in the design and delivery of culturally-responsive and effective substance abuse treatments. Culturally-responsive treatments are those that are sensitive to the specific treatment needs of members of special populations. This article presents specific issues and provides directions for the design, development, and implementation of more effective substance abuse treatments for clients from special populations. These important issues include: (1) the development of provider cultural competence, (2) the need to incorporate cultural variables into treatment, (3) issues in program adaptation, and (4) issues in the transfer of science to practice. Strategic models are presented to aid in conceptualizing these issues, and to further understand relationships between important cultural variables. Finally, further scientific research is encouraged that will contribute an empirical database that will test and further develop these strategic models, in the interest of enhancing the efficacy and effectiveness of substance abuse treatments as delivered to racial/ethnic minority clients, and to clients from other special populations.