This chapter describes the epidemiology of substance use among adolescents in the United States, with a primary focus on rates of use of illicit and licit drugs among nationally representative samples of adolescents in 8th, 10th, and 12th grades in the Monitoring the Future study. Prevalence rates of alcohol use, tobacco use, marijuana use, other illegal drug use, nonmedical use of prescription drugs, and use of unregulated substances (e.g., synthetic marijuana, inhalants) are reported. Subgroup differences by grade, gender, race/ethnicity, parental education, and college plans are examined. In addition, historical trends in substance use and attitudes regarding substance use are described. Documenting the rates of substance use in the adolescent population and monitoring historical changes in public health and behavior are critical for understanding the public health burden of adolescent substance use.