Although recent data suggest high levels of adherence to expanding antiretroviral therapy (ART) programmes in resource-limited settings, the culture-specific barriers to adherence are poorly understood. In a prospective observational study, we found that 1.2% of patients discontinued ART because of a belief in spiritual healing. Spiritual beliefs should be an important part of ART adherence counselling in resource-limited settings, requiring close collaboration between HIV care programmes and religious leaders to identify common goals and ensure successful treatment.