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Although close to half of the newborns admitted to neonatal intensive care units receive treatment for “hypotension,” the normal physiologic blood pressure range ensuring appropriate organ perfusion in the neonate is unknown. Thus, the decision to treat hypotension in the newborn is based on statistically defined gestational and postnatal age–dependent normative blood pressure values and physicians’ beliefs rather than on data bearing physiologic reference. Dopamine is the most widely used sympathomimetic amine in the treatment of neonatal hypotension, and it is more effective than dobutamine in raising blood pressure. Volume administration is less effective in the immediate postnatal period, and its extensive use is associated with significant untoward effects, especially in preterm infants. During the course of their disease, some of the sickest hypotensive newborns become unresponsive to volume and pressor administration. This phenomenon is caused by the desensitization of the cardiovascular system to catecholamines by the critical illness and relative or absolute adrenal insufficiency. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone substitution in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for pressor support in the critically ill newborn with volume-and pressor-resistant hypotension. Finally, despite recent advances in our understanding of the pathophysiology and management of neonatal hypotension, there are few data on the impact of the treatment on organ blood flow and tissue perfusion and on neonatal morbidity and mortality.