Five large clinical trials are in progress in the United States and Canada examining the efficacy and safety of inhaled nitric oxide (iNO) for persistent pulmonary hypertension of the newborn (PPHN) and severe respiratory failure in near-term and term infants. A large trial in France that includes premature infants is also under way. Neonatologists have shown great interest in the use of iNO as a selective pulmonary vasodilator, but in the United States and perhaps elsewhere, widespread application of this treatment outside of study sites will have to await completion of clinical trials. At the current pace, we expect it will take several years to enroll an adequate number of patients to address relevant outcome end-points.