The brain controls both the physiologic and the behavioral coping responses to daily events as well as major stressors, and the nervous system is itself a target of the mediators of those responses through circulating hormones. The amygdala and hippocampus interpret what is stressful and regulate appropriate responses. The amygdala becomes hyperactive in posttraumatic stress disorder (PTSD) and depressive illness, and hypertrophy of amygdala nerve cells is reported after repeated stress in an animal model. The hippocampus expresses adrenal steroid receptors. It undergoes atrophy in several psychiatric disorders and responds to repeated stressors with decreased dendritic branching and reduction in number of neurons in the dentate gyrus. Stress promotes adaptation ("allostasis"), but a perturbed diurnal rhythm or failed shutoff of mediators after stress ("allostatic state") leads, over time, to wear and tear on the body ("allostatic load"). Neural changes mirror the pattern seen in the cardiovascular, metabolic, and immune systems, that is, short-term adaptation versus long-term damage. Allostatic load leads to impaired immunity, atherosclerosis, obesity, bone demineralization, and atrophy of nerve cells in brain. Allostatic load is seen in major depressive illness and may also be expressed in other chronic anxiety disorders such as PTSD and should be documented.