This article summarizes the proceedings of a symposium at the 2005 Research Society on Alcoholism, Santa Barbara, California. The purpose of the symposium was to address challenges that arise in translating evidence for efficacy of alcohol brief intervention (BI) into diverse clinical settings and populations by reviewing the literature and describing 4 research studies. Dr. Saitz reviewed the limitations in evidence for efficacy of BIs and then described results of a randomized clinical trial of brief motivational intervention for medical inpatients drinking risky amounts. Dr. Svikis presented alternative methods for identifying pregnant women in prenatal care at risk for alcohol and drug problems (including nicotine and caffeine) and BIs to reduce or eliminate use. Dr. D'Onofrio discussed results of a randomized trial of the brief negotiated interview in emergency department patients. Dr. Kraemer presented results of a decision analytic and computer-simulation model regarding the cost-effectiveness of alcohol screening and intervention in primary care settings. Finally, Dr. Perl discussed the salient issues and suggested future directions for work in the area of alcohol BI.