Corticotropin-releasing hormone (CRH) plays a central role in the adaptation of the organism to stress. It serves as the main regulating hormone of the hypothalamic pituitary adrenal (HPA) axis, which is activated within seconds after exposure to acute stress. Furthermore, it acts as a neurotransmitter in numerous other brain regions. Globally, CRH leads to a number of metabolic, neuroendocrine and autonomic adaptations, which are vitally important for an adequate reaction to acute stress, but can lead to pathological somatic and psychological effects in chronic stress situations. The adequate functioning of CRH is a delicate equilibrium, which can be permanently disturbed by early experiences of physical or sexual abuse, leading to psychopathology in adulthood. This review discusses the physiological functions of CRH as the stress response hormone. Subsequently, the emerging data on the disruptive effects of early trauma on the CRH system are summarized. The third part is devoted to CRH and HPA axis abnormalities in major depression and other psychiatric disorders. This rapidly accumulating evidence will change our understanding of psychopathology, and might challenge the established classification of psychiatric disorders.