Substantial literature suggests that diverse biological, psychological, and sociocultural mechanisms account for differences by race and ethnicity in the experience, epidemiology, and management of pain. Many studies have examined differences between Whites and minority populations, but American Indians (AIs), Alaska Natives (ANs), and Aboriginal peoples of Canada have been neglected both in studies of pain and in efforts to understand its biopsychosocial and cultural determinants. This article reviews the epidemiology of pain and identifies factors that may affect clinical assessment and treatment in these populations. We searched for peer-reviewed articles focused on pain in these populations, using PubMed, CINAHL, Cochrane, and the University of New Mexico Native Health Database. We identified 28 articles published 1990-2009 in 3 topic areas: epidemiology of pain, pain assessment and treatment, and healthcare utilization. A key finding is that AI/ANs have a higher prevalence of pain symptoms and painful conditions than the U.S. general population. We also found evidence for problems in provider-patient interactions that affect clinical assessment of pain, as well as indications that AI/AN patients frequently use alternative modalities to manage pain. Future research should focus on pain and comorbid conditions and develop conceptual frameworks for understanding and treating pain in these populations.Perspective-We reviewed the literature on pain in AI/ANs and found a high prevalence of pain and painful conditions, along with evidence of poor patient-provider communication. We recommend further investigation of pain and comorbid conditions and development of conceptual frameworks for understanding and treating pain in this population.