The Neonatal Research Network developed and initiated 3 multicenter randomized controlled clinical trials evaluating inhaled nitric oxide therapy. Additional projects evolved from these efforts including basic science research and observational investigations. This article provides a historical prospective of the Network's investigations related to the diagnosis and management of neonatal hypoxic respiratory failure, especially those related to inhaled nitric oxide therapy. It will review the Network's contributions toward advancing the clinical care of the newborn with severe hypoxic respiratory failure.