Hageman, and Littlejohn have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/ device. Educational Gaps1. More long-term neurodevelopmental outcome studies are also necessary to determine the safety of treatment with hydrocortisone therapy. 2. There is reasonable evidence to suggest that relative adrenal insufficiency is a true entity in critically ill premature infants. 3. More research is necessary to further characterize transient vs permanent adrenal insufficiency in premature infants and to help in the decision-making process of which infants to treat with appropriate doses and dosing intervals of hydrocortisone therapy. AbstractManagement of critically ill very low-birth-weight infants with the clinical picture of vasopressor-resistant shock in the neonatal intensive care unit is a complex issue. Once airway and breathing have been stabilized and hypotension has been treated with volume and vasopressors with no improvement, the issue of cardiovascular insufficiency must be addressed. After cultures have been performed and antibiotic therapy started, the question of adrenal insufficiency arises. This article discusses of the development of the hypothalamic-pituitary-adrenal axis during gestation, aspects of what is considered normal function, and the diagnosis and management of the entity of relative adrenal insufficiency in the premature infant.Objectives After completing this article, readers should be able to:1. Understand the state of the art of relative adrenal insufficiency in the premature infant.