Adherence to antiretroviral therapy (ART) is often jeopardized by factors misapprehended by health-care providers. As South Africa is severely affected by HIV and AIDS, identifying factors that influence adherence in this specific context becomes essential. An exploratory and descriptive case study design was used to further explore this subject and to identify factors that could influence adherence to ART. A significant correlation with international data was found. Most participants indicated that their traditional beliefs and customs did not interfere with their adherence to ART, although the lack of HIV education might facilitate reversion to traditional customs. Adequate treatment preparation, comprehensive HIV education and a supportive patient–provider relationship seemed to impact adherence significantly.