The lack of frequent real-world opportunities to study preparedness for large-scale public health emergencies has hindered the development of an evidence base to support best practices, performance measures, standards, and other tools needed to assess and improve the nation’s multibillion dollar investment in public health preparedness. In this article, we argue that initial funding priorities for public health systems research on preparedness should focus on using engineering-style methods to identify core preparedness processes, developing novel data sources and measures based on smaller-scale proxy events, and developing performance improvement approaches to support the translation of research into practice within the wide variety of public health systems found in the nation. (Disaster Med Public Health Preparedness. 2008;2:247–250)