Beauty is not the only thing that lies in the eye of the beholder. Stress, too, has both perceived and real components, and like beauty, the concept of stress has evolved. I believe that the stress axis, as described by Hans Seyle, which involves the neurohormonal activation of the hypothalamic-pituitary-adrenal (HPA) axis, is constantly in "overdrive" for many people today. While some stress actually benefits the organism as a whole, this constant state of being in a perceived state of stress exacerbates myriad disease symptoms. The CRF system, the main driving force behind the HPA axis influences immune and non-immune cellular responses locally in the peripheral tissues that are distinct from those mediated by the action of CRF in the CNS.