Although there is a small but growing body of literature examining the psychopathology of anxiety among Native Americans, no data are available regarding the efficacy of empirically supported treatments for anxiety disorders among Native Americans. Moreover, exceptional challenges arise in adapting mainstream approaches to Native Americans, such as language barriers, contrasting beliefs about the cause and treatment of emotional illness between mainstream and traditional Native American culture, problems with homework compliance, allowing extra time for rapport building, and the need for a spiritual component in the treatment of anxiety disorders. Native Americans also confront the challenges of rural living and low socioeconomic status. The focus of this article is largely conceptual in nature, informed by the limited psychopathology data and the first author's experience with cognitive behavioral treatment protocols for anxiety disorders and the provision of mental health services to Native Americans. In this article, we highlight the unique challenges of adapting manualized anxiety treatments for Native American clients.