Exposure of an organism to stress leads to activation of the sympatho-adrenomedullary system and the hypothalamo-pituitary-adrenal axis. Consequently, levels of noradrenaline, peptides like vasopressin and CRH, and corticosteroid hormones in the brain rise. These hormones affect brain function at those sites where receptors are enriched, like the hippocampus, lateral septum, amygdala nuclei, and prefrontal cortex. During the initial phase of the stress response, when hormone levels are high, these compounds mostly enhance excitability and promote long-term potentiation. Later on, when hormone levels have subsided but gene-mediated effects of corticosteroids start to appear, the excitability is normalized to the pre-stress level, in the CA1 hippocampal area, but possibly less so in the dentate gyrus and amygdala. A disturbed balance between these early and late phases of the stress response as well as a shift toward the relative contribution of the dentate/amygdala pathways may explain why the normal restorative capacity fails in vulnerable people experiencing a life-threatening situation, which could contribute to the development of PTSD.