The biomedical model categorizes certain features of suffering and distress as depression.These same features may receive different conceptualizations within different cultural or religious systems.Islamic approaches to conceptualizing the features of distress, and providing care for persons who display these features may be overlayed on, merged with, or even distinguished from the dominant biomedical model.Clergy play roles as informal mental health helpers, particularly for religious persons.They may also serve as gatekeepers or conduits for facilitating referrals to formal healthcare practitioners.Five clerics at a faith-based organization that serves two small Muslim communities in South Africa were interviewed about their conceptions of suffering that the biomedical model labels as depression.Rooted in their local cultural perspectives, community involvement, religious practice, and help-giving to Muslim persons, social constructionist thematic analysis of interviews with them revealed a nomenclature that contained three main frameworks: (1) depression as a 'real' illness, (2) depression as spiritual destiny, and (3) depression as unallowable sadness.The biomedical view informed their conception of depression as a 'real' illness, and this idea served as the central framework onto which the other two conceptions were hinged.Clergy legitimized certain features of depression as a 'real' illness but indicated that religious illness beliefs cannot be bracketed when serving Muslim individuals.The implication of the study is that mental health practitioners, trained in biomedical ideas, cannot assume that the term 'depression' is understood in the same way within different contexts.Clergy can educate health practitioners about these conceptions to improve caregiving and adherence to biomedical interventions.