Despite our inability to appropriately define the gestational- and postnatal-age dependent normative values of blood pressure, hypotension is often been diagnosed and treated in preterm neonates especially during the transitional period. Although the perceived normal blood pressure values can be restored in the majority of preterm neonates by administration of volume and vasopressor-inotropes, some patients will not respond even to higher doses of vasoactive medications. In these neonates with so-called “vasopressor-resistant hypotension”, steroid administration is usually effective in increasing the blood pressure to the perceived normal range and decreasing vasopressor requirement. The etiology of vasopressor-resistant hypotension is thought to be a combination of transient adrenocortical insufficiency of prematurity and downregulation of the cardiovascular adrenergic receptors. In the clinical practice, hydrocortisone is used most frequently for the management of vasopressor-resistance. Importantly, low-dose hydrocortisone appears to improve blood pressure without compromising cardiac function or systemic perfusion in these patients. However, caution must be exercised when hydrocortisone is administered during the first postnatal week as significant side effects including gastrointestinal perforation may occur especially in infants co-exposed to indomethacin. In addition, although the available data on the lack of a documented impact of early low-dose hydrocortisone administration on brain development are encouraging, more and appropriately powered studies are needed to put this concern to rest.