The pursuit of evidence-based practice (EBP) within the mental health professions has contributed to efficacious clinical intervention for individuals struggling with mental health problems. Within the context of the EBP movement, this article reviews the treatment outcome literature for mental health interventions directed specifically toward American Indians and Alaska Natives experiencing psychological distress. Fifty-six articles and chapters pertaining to the treatment of Native Americans with mental health problems were identified, though the vast majority of these did not systematically assess outcomes of specified treatments for Native American clients under scientifically controlled conditions. Of just nine studies assessing intervention outcomes, only two were controlled studies with adequate sample sizes and interpretable results relative to the identification of EBP among American Indians and Alaska Natives. The advantages and limitations of EBP for treatment of Native American mental health problems are discussed.