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This report explores the current state of knowledge regarding inequalities and their effect on American Indian and Alaska Native children, underscoring gaps in our current knowledge and the opportunities for early intervention to begin to address persistent challenges in young American Indian and Alaska Native children's development. This overview documents demographic, social, health, and health care disparities as they affect American Indian and Alaska Native children, the persistent cultural strengths that must form the basis for any conscientious intervention effort, and the exciting possibilities for early childhood interventions.