This chapter highlights the neurobiology of the whole spectrum of defense responses to threats: near or distant, immediate or potential, physical or social. It focuses on vigilance, fight, flight, freeze, hide, cringe, submit, and avoid behaviors. When survival is threatened by physical injury, death, or social exclusion, the brain has well-established responses, immediate and sequential, to promote safety. These defense responses are based in the emotion-generating regions of the brainstem but are rapidly modified and modulated by the more developed and evolved cortical capacities. The chapter focuses on clinical observations, brain imaging studies in humans, and animal studies of responses to trauma to promote testable conclusions on the likely neurochemical mediators of the key components of posttraumatic stress disorders (PTSD). Chronic characterological changes arising from alterations in self-perception with guilt and shame, self-blame, feelings of ineffectiveness, and loss of trust are part of the long-term damage caused by early trauma.