Despite substantial evidence documenting the social patterning of disease, relatively little information is available on how the health care system can best intervene on social determinants to impact individual and population health. Announced in January 2016, the Centers for Medicare and Medicaid Innovation's (CMMI) Accountable Health Communities (AHC) initiative provides an important opportunity to improve the evidence base around integrated social and medical care delivery. To maximize learning from this large-scale demonstration, comprehensive evaluation efforts should focus on effectiveness and implementation research by supporting local, regional, and national studies across a range of outcomes. Findings from this demonstration could transform how, when, and which patients' health-related social needs are addressed within the health care delivery system. Such findings would strongly complement other initiatives to address social factors outside of health care.