Environmental events, both physical and emotional, can produce stress reactions to widely varying degrees. Stress can affect many aspects of physiology, and levels of stress, emotional status, and means of coping with stress can influence health and disease. The stress system consists of brain elements, of which the main components are the corticotropin-releasing hormone (CRH) and locus ceruleus (LC)-norepinephrine (NE)/autonomic systems, as well as their peripheral effectors, the pituitary-adrenal axis and the autonomic system, which function to coordinate the stress response. Activation of the stress system results in behavioral and physical changes which allow the organism to adapt. This system is closely integrated with other central nervous system elements involved in the regulation of behavior and emotion, in addition to the axes responsible for reproduction, growth and immunity. With current trends in stress research which focus on understanding the mechanisms through which the stress-response is adaptive or becomes maladaptive, there is a growing association of stress system dysfunction, characterized by hyperactivity and/or hypoactivity to various pathophysiological states. The purpose of this review is to 1) define the concepts of stress and the stress response from a historical perspective, 2) present a dynamic overview of the biobehavioral mechanisms that participate in the stress response, and 3) examine the consequences of stress on the physiologic and behavioral well-being of the organism by integrating knowledge from apparently disparate fields of science.