Although there has been a substantial effort to establish the beneficial effects of social support on health and well-being, relatively little work has focused on how social support influences physical health. This article outlines possible mechanisms through which support systems may influence the etiology of physical disease. I begin by reviewing research on the relations between social support and morbidity and between social support and mortality. I distinguish between various conceptualizations of social support used in the existing literature and provide alternative explanations of how each of these conceptualizations of the social environment could influence the etiology of physical disease. In each case, I address the psychological mediators (e.g., health relevant cognitions, affect, and health behaviors) as well as biologic links (e.g., neuroendocrine links to immune and cardiovascular function). I conclude by proposing conceptual and methodological guidelines for future research in this area, highlighting the unique contributions psychologists can make to this inherently interdisciplinary endeavor.