This chapter reviews the findings of human and animal studies which have characterized normal function in the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis, and then briefly describes post-traumatic stress disorder (PTSD)-associated abnormalities seen in each system. Neurobiological models of the structure, function and neurochemistry of the brain have evolved significantly as a result of recent input from findings of neuroimaging studies. In recent years several neurochemicals have been associated with resilience. In humans, neuroimaging studies of PTSD have primarily focused on the amygdala, the hippocampus, medial prefrontal cortex, and anterior cingulate cortex. Multidisciplinary studies that use neurochemical, neuroimaging, genetic, and psychosocial approaches may in the future clarify the complex relationships between genotype, phenotype, and psychobiological responses to stress. Pharmacological intervention aimed at treating early severe symptoms which are known to be predictive of later PTSD, such as excessive arousal, is one possible avenue of study.