Social determinants of health, which encompass social, behavioral and environmental influences on one’s health, have taken center stage in recent health policy discussions. While research indicates that greater attention to these non-medical factors may improve health outcomes and reduce health care costs, translating this evidence into actionable recommendations for policy makers and others has been challenging. This report, prepared by a team led by Elizabeth Bradley of the Yale Global Health Leadership Institute and Lauren Taylor of the Harvard Divinity School, evaluates and synthesizes the evidence base for interventions that address social determinants of health, with special attention to innovative models that may improve health outcomes and reduce health care costs and that may be applicable in the Massachusetts policy context. Based on this review, there is strong evidence that increased investment in select social services (e.g., housing support and nutritional assistance), as well as various models of partnership between health care and social services (e.g., integrated health care and housing services), can result in substantial health improvements and reduced health care costs for targeted populations.