The Secretary of the Department of Health and Human Services (HHS), through the Office of the Assistant Secretary for Preparedness and Response (ASPR), coordinates federal Emergency Support Function (ESF) #8 preparedness, response, and recovery actions. To address these needs, the ASPR can draw on trained personnel from a variety of sources, both from within and outside HHS. Among the resources under the domain of HHS is the Medical Reserve Corps (MRC), directed by the Office of the Civilian Volunteer Medical Reserve Corps (OCVMRC) in the Office of the Surgeon General. MRC units are community based and function as a way to locally organize and utilize medical and public health professionals, such as physicians, nurses, pharmacists, dentists, veterinarians, and epidemiologists. Nonclinical volunteers, such as interpreters, chaplains, office workers, legal advisors, and others, can fill logistical and support roles in MRC units. This article discusses locally controlled (Hurricanes Gustav and Ike) and federalized (Hurricanes Katrina and Rita) MRC activations, and it describes the advantages of using medical volunteers in a large-scale disaster response setting.