This article reviews the expanding body of literature that examines the mental health of HIV-affected children in sub-Saharan Africa. Focusing on primary research across disciplines and methodologies, the review examines the use of universalistic assumptions about childhood adversity and mental health in driving forward this body of research. Of the 31 articles identified for this review, 23 had a focus on the psychological distress experienced by HIV-affected children, while only 8 explored social psychological pathways to improved mental health, resilience and coping. The article argues that this preoccupation with pathology reflects global assemblages of definitions, understandings and practices that constitute the global mental health framework. While such a focus is useful for policy interventions and the mobilisation of resources to support children living in HIV-affected communities, it overshadows more culturally relevant and strengths-based conceptualisations of how mental health is understood and can be achieved in different parts of Africa. Furthermore, a continued focus on the psychological distress experienced by HIV-affected children runs the risk of medicalising their social experiences, which in turn may transform the social landscape in which children give meaning to loss and difficult experiences. The article concludes that mental health professionals and researchers need to take heed of the biopolitical implications of their work, and argues for more community-oriented and resilience-enhancing research that brings forward the voices of local people to inform interventions tackling the psychosocial challenges inevitably experienced by many children in sub-Saharan Africa.