Following surgery for congenital heart disease, patients develop a predictable and progressive decline in cardiac output known as low cardiac output syndrome. During low cardiac output states, a compensatory response to increase systemic perfusion occurs both innately and as part of the postoperative pharmacologic support strategies intended to increase or sustain adequate oxygen delivery. The result typically involves a rise in systemic vascular resistance and heart rate. These and other responses may actually limit the ability of the recently operated heart to provide sufficient cardiac output to meet the oxygen demands of the body. In order to improve systemic oxygen delivery, clinicians have increasingly employed systemic vasodilator therapy to reduce afterload and improve ventriculoarterial coupling. This review will summarize currently utilized pharmacologic agents that promote systemic vasodilation and improve cardiac output through afterload reduction. This article addresses the fourth of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".