ABSTRACTNewborns, and especially premature newborns, are at significant risk for developing hypotension in the first week or two after birth. The etiology of hypotension in the newborn may vary, but the very low birth weight and extremely low birth weight preterm infants are less likely to respond to conventional cardiovascular support when they develop hypotension. This article reviews the least conventional treatment using hydrocortisone for hypotension that is refractory to conventional volume replacement and/or vasopressor medications with the underlying assumption that sick and premature newborns have a relative or measured adrenal insufficiency. The addition of hydrocortisone in the treatment of hypotension in the newborn is becoming more common but is not universally advocated. However, the supportive evidence is growing, and, as reviewed, use of hydrocortisone requires judicious and cautious regard.