Recently, there has been increasing awareness of adrenal exhaustion/immuno-endocrine derangements in the chronically ill patients receiving intensive care. Hypotension refractory to the administration of fluid and vasopressors is frequently encountered. In low gestation newborns, the administration of hydrocortisone has been associated with improved hemodynamic stability. To gain an insight into the underlying mechanism of this phenomenon, the relevant literature from a combined search through MEDLINE and EMBASE was examined. Available evidence suggests that adrenal insufficiency/exhaustion in low gestation newborns may be a principal underlying factor for persistent ductus arteriosus and low systemic blood pressure that is unresponsive to vasopressor treatment. It is hypothesized that early postnatal hydrocortisone supplement would facilitate immuno-endocrine homeostasis and the attainment of hemodynamic stability, thereby minimizing the morbidity and mortality associated with inadequate perfusion in this extremely vulnerable population.