Sufficient organ blood flow of healthy newborn babies is maintained by relatively low systemic blood pressure. Premature infants are at an increased risk of systemic hypotension, often but not obviously, resulting in hypoperfusion of the cerebral, renal and intestinal vascular beds. Maintaining a stable blood pressure in preterm babies is of high importance in order to prevent complications such as intraventricular hemorrhage, periventricular leucomalatia, necrotizing enterocolitis or renal failure. The regulation of systemic and local hemodynamics in newborns differs substantially from that of the adults. Developmental changes in catecholamine sensitivity, higher local vasodilator factor activity and structural differences of the immature myocardium should be taken into account when applying vasoactive agents in neonates. The effects of widely used catecholamines such as dopamine, epinephrine or dobutamine can not be directly adapted from adult therapeutics to neonatal care. Their administration should be supported by data on their effects on systemic and cerebral blood flow in addition to blood pressure changes. At the bedside, neonatologists should use new diagnostic tools to differentiate between neonatal hypotension and hypoperfusion, vasoconstriction and myocardial dysfunction in order to choose the appropriate medication. Newer vasoactive agents already used in adult or pediatric cardiovascular therapy such as milrinone, levosimendan or terlipressin need to be carefully evaluated before introducing them to the treatment of neonatal hypotensive states. Welldesigned preclinical and human newborn studies also evaluating their local effects are warranted.