About 40 years since the first controlled study, screening and brief intervention (SBI) are being disseminated into practice. But many unanswered questions remain. Studies in this special issue address what we know and don't know about alcohol and drug SBI, cost-effectiveness, patient preferences, education for clinicians, quality performance measures, "no-contact" SBI, predictors of behavior change, and methodological concerns with the SBI literature. The best evidence for efficacy of SBI is that it can lead to decreased consumption in primary care patients with non-dependent unhealthy alcohol use. But further research is needed on brief drug screening tools, efficacy of SBI for drugs, effectiveness in real world settings, integration of SBI for alcohol and drugs with other health behaviors, effects of SBI on alcohol and drug consequences, effects on dependence among those not seeking help, and on how to best disseminate the efficacious elements of SBI into practice.