In the United States, use of alcohol and other drugs is associated with the three leading causes of death and disability (i.e., unintentional injuries, primarily from motor vehicle crashes; suicide; and homicide) among American Indian/Alaska Native (AI/AN) persons aged 15-24 years, and tobacco use is associated with the two leading causes of death (i.e., heart disease and cancer) among AI/AN adults. This report presents data about the prevalence of tobacco, alcohol, and other drug use among high school students at schools funded by the Bureau of Indian Affairs (BIA). The findings indicate that a substantial number of these students engage in behaviors that put them at risk for premature death and disability and underscore the need for expanded health education and counseling programs and policies in AI communities and BIA-funded schools.