There is a dearth of evidence on the relative efficacy of intervention modalities to improve and maintain patient adherence to antiretroviral medications. Although empiric findings from research on HIV/AIDS, other diseases, and chronic medical conditions consistently demonstrate that social support plays an important role in facilitating adherence, few HIV/AIDS interventions have directly targeted this factor. Ewart's social action theory emphasizes the role of social relationships in behavior change and provides a comprehensive and useful guide to the development of interventions for adherence. We describe the development, content, and testing of SMART Couples, an effective antiretroviral adherence intervention that is grounded in social action theory and designed to enhance social support for ART adherence. Finally, we discuss some of the challenges of translating findings from the randomized clinical trial of this intervention into clinical practice and offer recommendations for integration of lessons learned into ongoing clinical care.