‘Stress’ embraces the reaction to a multitude of poorly defined factors that disturb homeostasis or allostasis. In this overview, the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system have been utilized as objective measurements of stress reactions. Although long-term activation of the sympathetic nervous system is followed by primary hypertension, consequences of similar activation of the HPA axis have not been clearly defined. The focus of this overview is to examine whether or not repeated activation of these two stress centres may be involved in the pathogenesis of abdominal obesity and its comorbidities. In population studies adrenal hormones show strong statistical associations to centralization of body fat as well as to obesity. There is considerable evidence from clinical to cellular and molecular studies that elevated cortisol, particularly when combined with secondary inhibition of sex steroids and growth hormone secretions, is causing accumulation of fat in visceral adipose tissues as well as metabolic abnormalities (The Metabolic Syndrome). Hypertension is probably due to a parallel activation of the central sympathetic nervous system. Depression and ‘the small baby syndrome’ as well as stress exposure in men and non-human primates are followed with time by similar central and peripheral abnormalities. Glucocorticoid exposure is also followed by increased food intake and ‘leptin resistant’ obesity, perhaps disrupting the balance between leptin and neuropeptide Y to the advantage of the latter. The consequence might be ‘stress-eating’, which, however, is a poorly defined entity. Factors activating the stress centres in humans include psychosocial and socioeconomic handicaps, depressive and anxiety traits, alcohol and smoking, with some differences in profile between personalities and genders. Polymorphisms have been defined in several genes associated with the cascade of events along the stress axes. Based on this evidence it is suggested that environmental, perinatal and genetic factors induce neuroendocrine perturbations followed by abdominal obesity with its associated comorbidities.