Maintenance of a safe and stable health care infrastructure is critical to an effective mass casualty disaster response. Both secondary contamination during chemical disasters and hospital-associated infections during epidemic illness can pose substantial threats to achieving this goal. Understanding basic principles of decontamination and infection control during responses to chemical and biologic disasters can help minimize the risks to patients and health care workers. Effective decontamination following toxic chemical exposure should include both removal of contaminated clothing and decontamination of the victim's skin. Wet decontamination is the most feasible strategy in a mass casualty situation and should be performed promptly by trained personnel. In the event of an epidemic, infection prevention and control measures are based on essential principles of hand hygiene and standard precautions. Expanded precautions should be instituted as needed to target contact, droplet, and airborne routes of infectious disease transmission. Specific equipment and measures for critical care delivery may serve to decrease risk to health care workers in the event of an epidemic. Their use should be considered in developing comprehensive disaster response plans.