Persistent pulmonary hypertension of the newborn (PPHN) is a cardiopulmonary disorder characterized by systemic arterial hypoxemia secondary to elevated pulmonary vascular resistance with resultant shunting of pulmonary blood flow to the systemic circulation. PPHN is a serious illness that becomes progressively worse and is sometimes fatal. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilatation, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide (NO) has been one of the latest measures to successfully treat PPHN. If all other treatments fail, extracorporeal membrane oxygenation (ECMO) can be used. Recently, preclinical and clinical studies have demonstrated the utility of the selective inhibitor of phosphodiesterase type 5 (PDE5), sildenafil, in decreasing pulmonary hypertension (HP). Sildenafil was first employed to offset rebound pulmonary hypertension in infants upon withdrawal of NO treatment. Later, several case reports demonstrated the effectiveness of sildenafil in the treatment of PPHN. Two randomized blinded studies with sildenafil in infants with PPHN were published in 2006. In both studies, the patients treated with sildenafil showed a steady improvement in pulse oxygen saturation over time. Likewise, the frequency death was lower in the groups treated with sildenafil. Recent evidence shows the utility of sildenafil in the treatment of PPHN. However, since existing data are limited there is an urgent need for multicenter blinded, placebo controlled, randomized trials.