Deviations from emotional and physiological homeostasis in humans occur under episodic, chronic, or traumatic stress experiences. These dysregulations can provoke emotional and physical disturbances that may result in stress-related psychiatric or psychosomatic disorders. This brief review discusses a variety of both naturally occurring and experimental stressors and the complexity of intervening variables on cardiovascular and hormonal dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis. In addition to the type, intensity, and duration of the stressor, subject variables such as dispositional factors (e.g., age and sex), personality traits, and coping styles are considered. Finally, emotional and physiological stress responses to naturally occurring stressors and psychological challenge tests in depressed patients and anxiety disorder patients are presented and discussed. Stressors in humans induce emotional arousal, which leads to physiological activation of the central nervous system, an increase of hormones of the HPA axis, and coping reactions on the psychological and behavioral level. Depending on the type, intensity, and duration of the stressor, on personal and psychosocial resources of the individual, stressful situations may provoke emotional and physical disturbances. These dysfunctions may result in psychosomatic or psychiatric disorders. The following brief review intends to discuss a variety of stressors that have been examined in humans in order to gain insight into the complex relationship between physiological and behavioral stress reactions and the occurrence or maintenance of stress related psychosomatic and psychiatric disorders.