This chapter explores various clinical aspects of large-scale exposures to chemical agents, and presents several examples of both intentional and accidental events. It demonstrates the importance of rapid identification and treatment of those individuals with early acute respiratory failure. Several examples of events are followed by commentaries that include perspectives on the mitigation, preparedness, response, or recovery efforts for each event. Chemical agents used in a large-scale terrorist attack fall into four categories of compounds: pulmonary intoxicants, cyanides, vesicants, and nerve agents. Medical review of large-scale chemical events is necessary for purposes of quality improvement and to provide a database record to assist in validation of current medical practice and development of novel medical interventions. Federal Emergency Management Agency (FEMA) is responsible for developing preparedness plans, upgrading response capabilities, and conducting training for these civilian communities. These obligations were integrated into program called the Chemical Stockpile Emergency Preparedness Program (CSEPP).