The hormonal alterations observed during critical illness are extremely diverse, being both adaptive and maladaptive. Central and peripheral mechanisms are at play depending on the duration and severity of the insult. Perturbations in the endocrine axes are exacerbated by endogenous mediators and by pharmacologic intervention. The emergence of the concept of the wound, or inflammatory lesion, as an endocrine organ introduces new potential mechanisms of stress physiology and possible interventional strategies. Whether the physiology of the wound can be manipulated to heighten organism resistance to stress either emergently or electively is theoretically appealing and supported by animal models. Currently, however, it remains a subject of ongoing controversy and research.