The quality of one’s familial life, for better or worse, has been linked to physical health. Such associations are evident across a number of acute and chronic conditions and highlight the widespread impact that close relationships have on physical health. However, the field currently lacks a complete understanding of the integrative biological pathways underlying the association between close relationships and disease risk. This article reviews the main peripheral biological and central nervous system pathways linking positive and negative familial relationship processes to physical health outcomes. It emphasizes the role of neurochemical pathways in mediating the influence of social relationships on health-relevant peripheral physiological systems using the oxytocin system as a model. Such neurochemical approaches are an important step toward a more integrative understanding of complex biological pathways and has novel theoretical and intervention implications.