We review the development of a disaster health care response system in Mississippi aimed at improving disaster response efforts. Large-scale disasters generate many injured and ill patients, which causes a significant utilization of emergency health care services and often requires external support to meet clinical needs. Disaster health care services require a solid infrastructure of coordination and collaboration to be effective. Following Hurricane Katrina, the state of Mississippi implemented best practices from around the nation to establish a disaster health care response system. The State Medical Response System of Mississippi provides an all-hazards system designed to support local response efforts at the time, scope, and scale required to successfully manage the incident. Components of this disaster health care response system can be replicated or adapted to meet the dynamic landscape of health care delivery following disasters. (Disaster Med Public Health Preparedness. 2017;11:600-604).