This article summarizes current knowledge about the accuracy of screening tests and the efficacy of interventions for substance use disorders in different medical settings (including trauma centers) where the practitioners are not specialists in the management of substance use disorders. In the first section, we introduce basic screening approaches for psychoactive substance use disorders and issues of natural history, risk factors, and populations at risk. Next, we review recent scientific research on the development of screening tests and the evaluation of early intervention services for persons at risk. We conclude that reliable and valid screening tests are available to detect alcohol use disorders but that further work is needed before routine screening for drug use disorders is warranted. We found strong evidence to support the effectiveness of brief interventions in managing at-risk drinkers; however, the evidence is only suggestive for drug use disorders. Finally, we explore the implications of the findings for developing a public health approach to early intervention, particularly as it relates to the unique needs of trauma centers.