Health disparities research in the United States over the past 2 decades has yielded considerable progress and contributed to a developing evidence base for interventions that tackle disparities in health status and access to care. However, health disparity interventions have focused primarily on individual and interpersonal factors, which are often limited in their ability to yield sustained improvements. Health disparities emerge and persist through complex mechanisms that include socioeconomic, environmental, and system-level factors. To accelerate the reduction of health disparities and yield enduring health outcomes requires broader approaches that intervene upon these structural determinants. Although an increasing number of innovative programs and policies have been deployed to address structural determinants, few explicitly focused on their impact on minority health and health disparities. Rigorously evaluated, evidence-based structural interventions are needed to address multilevel structural determinants that systemically lead to and perpetuate social and health inequities. This article highlights examples of structural interventions that have yielded health benefits, discusses challenges and opportunities for accelerating improvements in minority health, and proposes recommendations to foster the development of structural interventions likely to advance health disparities research.