Increasingly, it is recognized that traditional narrow approaches to environment and health relations are insufficient to comprehend and respond effectively to the complexity of factors influencing human health. In response, a new approach, referred to as Ecohealth has emerged with the goal of assessing the multiple interactions that occur between components the ecosystem, the local and global political economy, and cultural systems, on the one hand, and the ways in which these biosocial interactions influence the nature, concentration, and entwinement of health problems in human populations, on the other. Those contributing to the development of the Ecohealth orientation also seek to identify evidence-based strategies for improving the health and living conditions of human populations and the sustainability of the ecosystems in which they live. Within anthropology and public health, in particular, one reflection of the broader Ecohealth approach is expressed in the concept of syndemics, which was developed during the 1990s to label the various interactions among comorbid diseases and other health conditions that increase the burden of suffering in populations and the encompassing social relations and conditions that amplify the likelihood of adverse disease interactions occurring. In southern Africa, a notable synergism has developed between HIV/AIDS and food insecurity that significantly threatens the health and well-being of diverse populations in the region. The purpose of this chapter is to examine the key epidemiological, environmental, social, and political economic features of the entwined HIV-affected food insecurity and food insecurity-affected HIV syndemics of southern Africa.