Over several years, the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), supported research to determine the best process for emergency decontamination of victims from chemical exposure. This research included laboratory and human clinical studies and resulted in the publication of several peer-reviewed papers on effective procedures for decontamination, and the development of the Primary Response to Incident Scene Management (PRISM) decontamination guidance. This presentation will provide attendees with an overview of the research supporting the PRISM guidance, review the operational procedures for mass casualty chemical decontamination, and discuss the evolution of the recently released PRISM education curriculum. The PRISM guidance is part of BARDA’s advanced research and development portfolio of medical countermeasures to prevent, diagnose, and treat the U.S. population against chemical, biological, radiological, and nuclear threats.