Psychological and physical challenge leads to activation of the organism’s stress response systems. One of the major physiological stress response systems is the hypothalamus-pituitary-adrenal (HPA) axis. The HPA axis is a central regulatory and control system that connects the central nervous system with the endocrine system and regulates the secretion of glucocorticoids (GCs, cortisol in humans). Alterations of HPA axis stress responses appear to be a close correlate or even determining factor of the onset of different disease. Dysregulations of the HPA axis have been observed in various psychiatric illnesses including major depression, bipolar disorder, schizophrenia, anxiety disorders and post-traumatic stress disorder (PTSD). There is considerable inter-individual variability in HPA axis responsivity, and it has been demonstrated that stress reactivity in adulthood is influenced by genetic background.