Little is known about the patient characteristics, social support networks, and relationship factors associated with excellent adherence in resource-limited settings, even though these can be important clues that inform the identification of targets and the approaches of individual- and community-based antiretroviral therapy adherence interventions. In this study, we aimed to understand how patient-selected treatment supports might affect antiretroviral treatment outcomes and to identify key components of support, including the social and material resources necessary for promoting high adherence in South Africa. Data were collected from the proceedings of 2 focus groups with 6 HIV-infected adults each and from 7 in-depth interviews with health care providers in the Western Cape Province of South Africa. The patients and health care workers identified individuals-usually a mother, daughter, sister, brother, or partner-who were confidantes and had moral authority with them. These individuals command respect, and patients allow them to influence health-related decision making, both of which are necessary if they are to be effective treatment supporters. Barriers to adherence identified by study participants include alcohol abuse, stigma related to disclosure of HIV status, and lack of financial resources and food. These are critically important challenges to address if high adherence is to be achieved in this setting. In addition, our results suggest that interventions tailored to treatment supporter characteristics and relationship factors may be effective in influencing patients' antiretroviral therapy adherence.