The study emanates from the need to identify the biopsychosocial factors that influence patients’ adherence to antiretroviral therapy (ART) within the South African context The specific goal of the study was to explore these in order to make recommendations to enhance service delivery. Applied research was conducted, with its primary task being to stimulate thought and action concerning the challenges faced by patients who are on ART. In order to gather comprehensive data, the researcher engaged in a combination of the qualitative and quantitative approaches. For the qualitative case study the researcher made use of semi-structured interviews, utilizing the non-probability sampling method, aiming to understand and interpret the meaning that the multidisciplinary team accorded to matters of antiretroviral treatment. For the quantitative part of the study the probability random sampling method was made use of for the quantitative descriptive survey. Questionnaires were employed to collect data from 201 patients already on antiretroviral medication. The conclusions, which were drawn from the research findings, identified challenges to adherence to ART: the study confirmed that since the advent of combination antiretroviral therapy (HAART), HIV/AIDS has been transformed into a manageable and chronic condition, and has undoubtedly extended and improved the quality of life for people living with HIV/AIDS. However, it also confirmed that ART, is a complex intervention, which is accompanied by severe biopsychosocial implications, requiring near-perfect adherence in order to prevent the development of resistance. The impact that the various psychosocial needs of millions of HIV/AIDS people living on ART will have on current social structures and services, will tax the available professional social services, particularly the social work profession. The social correlation of HIV/AIDS and poverty is endorsed by the findings, confirming that the high level of unemployment, coupled with families who are headed by women and who receive little support, lead to almost total dependency on social security. The findings further indicate a specific relationship between socio-economic circumstances and the ability to adhere to ART. Empowering HIV/AIDS patients, to be able to adhere to ART, is therefore indicated, as is the further need for a regulator of HIV/AIDS support services, in order to protect and promote high standards of service delivery, especially counselling.