Indigenous children and families in the United States and U.S. territories are from communities with rich histories of culturally grounded knowledge and practices that are intended to guide their development and well-being. However, these communities have faced centuries of inequity and injustice that continue today. Child Trends’ Indigenous Children and Families initiative aims to work in partnership with Indigenous Peoples to address adverse current community conditions stemming from historical and ongoing colonization and resulting in intergenerational trauma. Our work draws on Indigenous culture as a protective factor and strength for healing and promoting community resilience to advance the well-being of children and families. We partner in research with Tribal Nations and organizations, academic/university research centers, foundations, and the federal government.