An important focus of recent calls for interdisciplinary approaches in health research has been the integration of social and biomedical sciences in understanding the causes of ill-health. Typical models for the incorporation of social factors into biomedical research include social factors as distal antecedents of more proximate biologic factors and gene-environment interaction. Under both models the distinction between social and biologic factors remains clear-cut, and consideration of social factors is not indispensable for understanding the biologic processes leading to disease. However, recent evidence suggests that social and biologic processes are inextricably linked in systems. This paper reviews models for the incorporation of social factors into the study of health, discusses the potentialities of systems approaches, and highlights implications for population health and epidemiology.