Health disparities exact a devastating toll upon Indigenous people in the United States. However, there has been scant research investment to develop strategies to address these inequities in Indigenous health. We present a case for increased health promotion, prevention, and treatment research with Indigenous populations. providing context to the recent NIH investment in the Intervention Research to Improve Native American Health (IRINAH) network. We discuss the disproportionate costs and consequences of disparities borne by Indigenous groups, the limited evidence base on effective intervention for this population, how population uniqueness often makes transfer of existing intervention models difficult, and additional challenges in creating interventions for Indigenous settings. Read more.