Social determinants of health have a profound impact on health status and the prevalence of health disparities in the United States. Significant improvements in national health indices are not possible without addressing social determinants of health. Drawing on their historical legacy as patient advocates, patient care expertise, and community focused education, nurses are ideally positioned to lead the nation in strategies to promote health equity. Nurses can embrace this new leadership role through the use of interdisciplinary collaboration, advocacy, political involvement, and community partnerships.