Disparities in health status and health outcomes for American Indian and Alaska Native (AIAN) populations have been recognized for nearly 500 years. This chapter focuses on three of the disparities that affect AIAN populations most heavily or in ways not seen among other racial/ethnic minority groups: alcohol and substance abuse, diabetes, and violence. It discusses the diversity of AIAN populations and describes historical injustices against AIAN populations and their relationship to health outcomes. The chapter then defines and describes how historical trauma impacts health equity for AIAN populations. It also describes the presence, predictors, and protective factors for disparities in alcohol/substance abuse, diabetes, and violence for American Indian and Alaska Native populations. Finally the chapter presents best-practice approaches for achieving health equity among AIAN populations.