This Funding Opportunity Announcement (FOA) encourages grant applications for Countermeasures Against Chemical Threats (CounterACT) Research Centers of Excellence (U54s). The mission of the CounterACT U54 program is to develop new and improved therapeutics for chemical threats. Chemical threats are toxic chemicals that could be used in a terrorist attack or accidentally released from industrial production, storage or shipping. They include traditional chemical warfare nerve agents such as sarin and VX, and toxic industrial chemicals and pesticides such as cyanide, chlorine, parathion, and sodium fluoroacetate. The scope of the research to be supported includes target and candidate identification and characterization, through candidate optimization and demonstration of in vivo efficacy, through Investigational New Drug (IND) submission and Phase 1 clinical trials when appropriate. Each new CounterACT Research Center of Excellence will be composed of an administrative core, scientifically related research and development subprojects, and scientific cores if needed and justified. Applicants must demonstrate that the formation of an interdisciplinary Center will produce a synergistic research environment that allows each project to share the creative strengths and resources of the others. Research and development plans must include milestones that create discrete go or no-go decision points in a progressive translational study plan.