Given that antiretroviral (ARV) medication adherence has been shown to be high in resource-limited countries, the question remains as to whether adherence will remain at that level as medications become more widely available. Comparing adherence to tuberculosis (TB) medications, which have been readily available, and ARV medications may help to indicate the likely future adherence to ARVs as access to these medications becomes more widespread. This study examined sense of coherence, social support, symptom status, quality of life, and adherence to medications in two samples of individuals being treated either for TB or human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) at clinics in Durban, South Africa. Findings revealed the distinctive socio-economic backgrounds of the two cohorts. Although there were significant differences with regard to the psychosocial variables, there were no significant differences by the two samples in adherence to medications as well as adherence to appointments. Given the self-selected nature of the participants in this study, namely those able to attend clinic, as well as those likely to be adherent to ARVs, there is every reason for caution in the interpretations of these findings. As access to ARV medications becomes more widely available in South Africa, the question remains as to whether such high adherence will be maintained given the constraints of access to food and other basic necessities.