Many patients with congenital heart disease and systemic-to-pulmonary shunts develop pulmonary arterial hypertension (PAH), particularly if the cardiac defect is left unrepaired. A persistent increase in pulmonary blood flow may lead to obstructive arteriopathy and increased pulmonary vascular resistance, a condition that can lead to reversal of shunt and cyanosis (Eisenmenger syndrome). Cardiac catheterization is crucial to confirm diagnosis and facilitate treatment. Bosentan is the only medication to date to be compared with placebo in a randomized controlled trial specifically targeting congenital heart disease-associated PAH. Lung transplantation with repair of the cardiac defect or combined heart-lung transplantation is reserved for recalcitrant cases.