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Background: Stress is essential for our health and resilience, but vulnerability to psychopathology is increased when the action of a chronic stressor becomes excessive, prolonged or inadequate., Method: This survey reviews the literature on the role that the hypothalamic-pituitaryadrenal (hpa) system plays in the neurobiology of stress. Corticotropin-releasing hormone (crh), vasopressin, adrenocorticotropin hormone (acth) and beta-endorphin are very important in the stress reaction. In this paper the focus is on cortisol action in the brain. results Cortisol is secreted by the adrenal cortex in hourly pulses and constantly following stress. The action of cortisol is mediated by binding two types of receptor proteins which influence gene transcription, namely mineralocorticoid receptors (mr) and glucocorticoid receptors (gr). mr and gr are located primarily in the hippocampus, amygdala and prefrontal cortex which regulate emotion and cognition. mr and gr are important for energy metabolism and regulate daily and sleep-related events. During stress, mr in coordination with other signals determines the defense against the stressor, hereas gr assists with the recovery and processing of stressful information and the storage of the experience in the memory., Conclusion: Heightened vulnerability to stress-related psychopathology arises when an imbalance occurs between the mr-activating and the gr-suppressing components of the stress reaction. The balance depends on the ability to cope with stress, which in turn depends on genetic factors interacting with the outcome of previous stressful experience.