BACKGROUND: As ART programmes in African settings expand beyond the pilot stages, adherence to treatment may become an increasing challenge. This qualitative study examines potential barriers to, and facilitators of, adherence to ART in a workplace programme in South Africa. METHODS: We conducted key informant interviews with 12 participants: six ART patients, five health service providers (HSPs) and one human resources manager. RESULTS: The main reported barriers were denial of existence of HIV or of one's own positive status, use of traditional medicines, speaking a different language from the HSP, alcohol use, being away from home, perceived severity of side-effects, feeling better on treatment and long waiting times at the clinic. The key facilitators were social support, belief in the value of treatment, belief in the importance of one's own life to the survival of one's family, and the ability to fit ART into daily life schedules. CONCLUSION: Given the reported uncertainty about the existence of HIV disease and the use of traditional medicines while on ART, despite a programme emphasising ART counselling, there is a need to find effective ways to support adherence to ART even if the individual does not accept biomedical concepts of HIV disease or decides to use traditional medicines. Additionally, providers should identify ways to minimize barriers in communication with patients with whom they have no common language. Finally, dissatisfaction with clinical services, due to long waiting times, should be addressed.