Background: Anecdotal and empirical evidence seems to indicate that many people across the African continent indulge in different cultural practices that impinge on their adherence to the Highly Active Antiretroviral Therapy (HAART). These cultural practices vary between ethnicities or regions. Objective: The aim of this paper was to explore the cultural practices affecting HIV positive patients’ adherence to HAART in the Mopani district in Limpopo province, South Africa. Methods: A qualitative, explorative, descriptive study was conducted. Data were collected through one-to-one unstructured interviews using an interview schedule guide. Data were analysed using Tesch’s method of qualitative data analysis. Results: The findings indicate that cultural practices and beliefs concerning diseases and cure, prevailing faith that traditional health practitioners (THPs) could treat HIV/AIDS, stigmatisation of HIV patients, and the belief that HIV is caused by witchcraft and demons were the factors affecting patients on HAART. Clearly, HIV positive patients on HAART concurrently visit and patronise the THPs. This practice is affected by their cultural orientations and negatively impact on their adherence to HAART. Conclusion: The increased patronage of traditional medicine among HIV individuals are HAART calls for the integration of traditional health services into public health, and a multi-disciplinary collaboration would be beneficial to the community.