The success of antiretroviral therapy (ART) for HIV infection, though widespread and resounding, has been limited by inadequate adherence to its unforgiving regimens, especially over the long term. This article summarizes the literature on behavioral interventions to promote ART adherence and highlights some of the most recent and innovative research on patient education and case management, modified directly observed therapy, contingency management, interventions emphasizing social support, and novel technologies to promote awareness. Research in the area of adherence in pediatric HIV infection and in resource-constrained international settings also is considered. Although adherence interventions have been successful in experimental trials, they may not be feasible or adaptable given the constraints of real-world clinics and community-based settings. Implementation and dissemination of adherence interventions needs increased attention as ART adherence research moves beyond its first decade. We conclude with suggestions for incorporating research findings into clinical practice.