Using perspectives from medical and urban anthropology, we examine the phenomenon of hypermarginality--the clustering of extreme poverty, chronic disease, addiction, violence and trauma in certain social and spatial contexts, often urban. We will explore both the broader social, political, and economic structures of exclusion that produce hypermarginality, as well as the illness experiences associated with these conditions. As we consider both social suffering and the related institutional responses, we will also discuss the role of anthropological approaches in national discussions about health inequities.