National health guidelines provide policy makers and the public with recommendations for various behavioral factors known to promote health and reduce disease risk, such as diet and physical activity. Given public health concerns about social isolation, loneliness, and other forms of lacking social connection, the evidence supports establishing national health guidelines for “social connection.” The aggregate body of scientific evidence demonstrates social connection protects health and reduces health risks, pointing to clear relevance for public health. Taken together with national trends suggesting greater social disconnection, there is a compelling case for national preventative efforts. This article summarizes evidence on the health relevance of social connections, potential opportunities, and challenges in establishing and implementing guidelines, the process of establishing guidelines, and provides illustrative evidence-based examples of potential recommendations.