Although health services work towards improving conditions of children living in poverty in resource-poor countries affected by the HIV and AIDS epidemic, progress towards these goals is complicated not only by the negative impact of disease but also social and economic circumstances. Theories that are used to guide intervention must, therefore, account for the multicausal origins of developmental lag. The data that have been used to develop intervention are primarily from research conducted in developed nations, where the risk factors are less intense and support services are more accessible to children. This chapter proposes ways for research to account for development of children living in communities affected by poverty and HIV. The suggested methods of research integrate a co-constructivist model, which acknowledges the interplay of biological and cultural factors and addresses the complexity of human development. This chapter focuses on the circumstances of a specific geographic context, the KwaZulu-Natal province in South Africa, to demonstrate how child development can be complicated by poverty and disease.