Translating research evidence to reduce health disparities has emerged as a global priority. The 2008 World Health Organization Commission on Social Determinants of Health recently urged that gaps in health attributable to political, social, and economic factors should be closed in a generation. Achieving this goal requires a social determinants approach to create public health systems that translate efficacy documented by research into effectiveness in the community. We review the scope, definitions, and framing of health disparities and explore local, national, and global programs that address specific health disparities. Such efforts translate research evidence into real-world settings and harness collaborative social action for broad-scale, sustainable change.