Adolescence is a distinct and highly vulnerable period of neurodevelopment, which is particularly sensitive to substance use exposure. Furthermore, many of the intervention approaches that are currently employed with adolescent substance use behavior are ones that have been developed for adults, and then implemented with adolescents. Studies have found that adolescents are substantially less responsive to these behavioral intervention approaches than their adult counterparts. At the same time, adolescence is a critical crossroads; interventions that can effectively place adolescents back onto a path of health and development are likely to have long-term benefits for high risk and high need youth. Under the oversight of key CASAA investigators, research in this area is dedicated to identifying factors that may place adolescents at risk, as well as factors that may influence youths' response to prevention and intervention approaches. Together, this information aims to help us directly improve the growth and development of adolescents.