First responders, including military health care workers, public health service workers, and state, local, and volunteer first responders serve an important role in protecting our nation's citizenry in the aftermath of disaster. Protecting our nation's health is a vital part of preserving national security and the continuity of critical national functions. However, public health and public safety workers experience a broad range of health and mental health consequences as a result of work-related exposures to natural or man-made disasters. This chapter reviews recent epidemiologic studies that broaden our understanding of the range of health and mental health consequences for first responders. Evidence-based psychopharmacologic and psychotherapeutic interventions for posttraumatic distress reactions and psychiatric disorders are outlined. Finally, the application of public health intervention models for the assessment and management of distress responses and mental disorders in first-responder communities is discussed.