Experimentation with alcohol and other drugs (AOD) is commonplace among American adolescents. Despite reduction efforts, the use of AOD by adolescents has increased over the past decade. A number of youth experience significant negative personal, societal, economic, and health ramifications, but continue to abuse AOD and develop substance use disorders (SUD). Accurate assessment of adolescent AOD use is essential in determining the prevalence of SUDs, the development of effective interventions, and the implementation of beneficial prevention initiatives. Developmental considerations are significant factors in the validity of youth AOD assessment and are detailed in this chapter.