Substance use is the most common health risk behavior among adolescents and is one of the greatest threats to their current and future health. Universal screening of adolescents in general medical settings can be instrumental in identifying substance use early, before further problems develop and when BIs are more likely to be effective. Screening in and of itself may have some therapeutic effect. Brief screening tools feasible for use by busy medical offices to quickly and reliably assess adolescent risk for a substance use disorder now are available. A recent study found that a physician-conducted CRAFFT screen interview required an average of 74 seconds to complete, whereas a computer self-administered version took an average of 49 seconds. The CRAFFT and AUDIT tools currently have the most evidence for validity among adolescents, whereas the validity of other widely used tools such as DAST-10, NIDA-modified ASSIST (Alcohol, Smoking and Substance Involvement Screening Test), and ultra-brief screens (AUDIT-C, single-item screens) has yet to be established for adolescents. Studies are needed to identify effective strategies to promote universal adolescent screening and the use of valid screening tools in general medical settings. One statewide (Massachusetts) study found that although most (86%) primary care physicians seeing adolescents reported screening adolescents for substance use annually, only 1 in 3 reported using a validated tool (the CRAFFT). The remaining physicians reporting using informal screening procedures, their own questionnaire, or the CAGE. Computerization of screening and integration into the electronic health record appear to be promising strategies to promote universal screening and standardized use of valid screening tools. Increasing adolescent screening rates necessitates supporting physicians' ability to respond effectively to the screen results. To that end, recent evidence-informed practice guides from the AAP and NIAAA provide a structured algorithm for specific recommended responses based on level of risk. Adolescents who are at low or moderate risk for a substance use disorder, who constitute most of those seen in general medical settings, may be effectively counseled with a few minutes of brief advice, particularly after being primed with screening, feedback, and education before seeing their physician. High-risk patients (screen-positives) should receive a brief follow-up assessment to determine the appropriate level of care needed and a BI, using MI principles, to enhance motivation for behavioral change and help-seeking. Indications of acute danger or addiction may necessitate breaking confidentiality to protect patient safety and begin RT. Our review shows a small but growing body of research on the effectiveness of opportunistic BIs following screening of adolescents in clinical settings. Studies to date have largely tested brief alcohol-focused MI-based interventions with adolescents in the ED or trauma care settings; however, the number of studies conducted in primary health care settings is increasing. The strongest BI effects found in these studies tend to be related to harm reduction, such as reduction of substance-related driving/riding, alcohol-related injuries, unplanned sex, and other negative consequences of use. Effects on substance use have been more modest and tend to be stronger at shorter (< or = 6 months) rather than longer follow-up (> or = 12 months). However, many of these studies compared BI to active control conditions, which often included elements of BI (eg, assessment, brief advice, informational handouts). Significant reductions in substance use and related harms were also seen in these control groups, likely making detection ofa BI effect more difficult. A few studies have shown initial support for a prevention effect of BI among abstinent adolescents. At the opposite end of the spectrum, little is known about the effects of BI for adolescents with dependence and needing RT because of a lack of studies. Other areas needing additional research are the effect of BI on adolescent drug use, particularly on use of drugs other than cannabis; the mediators and moderators of BI effects; ways to reinforce and sustain effects over time; and how best to increase SBI implementation in general medical settings and to effectively train physicians. The effect of efforts such as the Substance Abuse and Mental Health Services Administration-funded physician residency SBIRT training programs remain to be determined. There has been increasing investigation into the potential of interactive computer technologies to aid SBIRT delivery to adolescents and young adults. A more detailed review of this area of research is beyond the scope of this article, but computer technology is proving to be an acceptable and effective tool in the delivery of BIs to young people, both as physician "extenders" in clinical settings and in the form of stand-alone self-guided programs. Computer technologies likely will play a critical role in promoting the expansion of SBIRT implementation for youth in general medical settings.