Recent experimental and clinical data demonstrate that both hypocapnia and hypercapnia during the neonatal period may result in beneficial or adverse consequences. Multiple retrospective studies report a strong association between PaCO2 levels less than 25 to 30 mm Hg and an increased incidence of cystic PVL and CP in preterm infants. Prolonged exposure to PaCO2 values less than 25 to 30 mm Hg is also associated with hearing loss in term and near-term infants. A low tidal volume strategy combined with permissive hypercapnia is potentially a strategy that could prevent lung injury. Clearly, more randomized, controlled trials are needed before this latter strategy or that of permissive hypercapnia can be recommended routinely for preterm, near-term, or term gestation infants with respiratory disorders.