Social interactions can profoundly affect the hypothalamic-pituitary-adrenal (HPA) axis. Although most research on social modulation of glucocorticoid concentrations has focused on the consequences of exposure to stressful social stimuli, there is a growing body of literature which suggests that social support in humans and affiliative behaviors in some animals can provide a buffer against stress and have a positive impact on measures of health and well-being. This review will compare HPA axis activity among individuals for whom social relationships are maintained through aggressive displays, such as dominance hierarchies, vs. individuals engaging in high levels of prosocial behavior. We also will examine oxytocin, a neuropeptide that is well known for promoting social behavior, as the physiological link between positive social interactions and suppression of the HPA axis. Despite many examples of social interaction modulating the HPA axis and improving health outcomes, there is relatively little known regarding the underlying mechanisms through which social behavior can provide a buffer against stress-related disease.