In this chapter, we review the ways in which social relationships help offset the cost of many of life’s effortful activities, including the activities of the human brain. In our discussion, we emphasize the management by social proximity and interaction of prefrontal resources devoted to vigilance, working memory, and self-regulation. We then contrast two models—the down-regulation model and the social baseline model—of potential neural mechanisms linking the social regulation of emotion to decreased threat responding, and we review the evidence supporting the two views. The down-regulation model emphasizes regulatory circuits within the prefrontal cortex and elsewhere that mediate associations between social contact and decreased subcortical threat responding. The social baseline model views social contact as closer to the human brain’s “baseline” state of relative calm, positing no mediation by regulatory circuits of the decrease in threat related processing during social contact. In discussing the social baseline model, we review principles of human behavioral ecology, such as economy of action, budgeting, risk distribution, and load sharing, which may have shaped human perceptual and regulatory capabilities to be intensely social in nature. Finally, we discuss the possible roles of oxytocin, the dorsal anterior cingulate cortex, and endogenous opioids in the social regulation of emotion.