This chapter begins with a discussion of general factors with a potential impact on the assessment and treatment of American Indian and Alaska Native people (AI/ANs). The history of AI/ANs is briefly summarized and followed by a description of the unique demographic, socioeconomic, and health characteristics of the population. Some common cultural values among AI/ANs are then outlined. The chapter concludes with a shift to specific recommendations and guidelines to aid clinicians in accurately assessing and successfully working with AI/ANs.