The alarming prevalence of suicidal behaviors in Native American communities remains a major concern in the 21st-century United States. Recent reviews have demonstrated that prevention programs and intervention efforts using transactional-ecological models have effectively reduced suicidal behaviors in the American Indian and Alaska Native populations sampled. As a result, this article adopts a transactional-ecological framework for conceptualizing suicidality and identifying points of intervention. Drawing on the most current empirical reports, the epidemiology of Native American suicidal behaviors is reviewed, while situating risk and protective factors within a biopsychosocial framework. Opportunities for intervention are discussed with a focus on the interactions between individuals and their environments, and the antecedent conditions leading to zones of heightened suicide risk.