OBJECTIVES: This article proposes a new stress-coping model for American Indians and Alaska Natives (AIs) that reflects a paradigmatic shift in the conceptualization of Native health. It reviews sociodemographic information on AIs, rates of substance abuse and related health outcomes, and the research supporting the model's pathways. OBSERVATIONS: Although health outcomes among AIs are improving, large disparities with other racial and ethnic groups in the United States remain. Many health-related problems are directly linked to high rates of substance use and abuse. CONCLUSION: Eurocentric paradigms focus on individual pathology. An "indigenist" perspective of health incorporates the devastating impact of historical trauma and ongoing oppression of AIs. The model emphasizes cultural strengths, such as the family and community, spirituality and traditional healing practices, and group identity attitudes.