This article provides an overview of the clinical evaluation and clinical treatment on multiple levels of American Indian, Alaskan Native, Native Hawaiian, and Pacific Islander youth, and their families. Included are basic cultural beliefs and practices shared among multiple tribes and nations within this diaspora, where the most important concept is balance and harmony in healing. Readers are provided with current practice approaches to core issues of substance abuse, anxiety, depression, and suicidal ideation including case examples, psychopharmacology, and therapy.