The authors consider the challenges to quantifying both the business case and the social case for addressing disparities, which is central to achieving equity in the U.S. health care system. They describe the practical and methodological challenges faced by health plans exploring the business and social cases for undertaking disparity-reducing interventions. Despite these challenges, sound business and quality improvement principles can guide health care organizations seeking to reduce disparities. Place-based interventions may help focus resources and engage health care and community partners who can share in the costs of—and gains from—such efforts.