There are physiological rationale and experimental data that suggest permissive hypercapnia and/or permissive hypoxemia may be well tolerated and result in reduced lung injury. Controlled studies in neonates report potential benefits of both permissive hypercapnia and permissive hypoxemia. The limited randomized controlled trials assessing early short-term postnatal use of permissive hypercapnia demonstrate positive or neutral results. The trials of permissive hypoxemia enrolled infants after the first week of life and also reported positive or neutral results. There is a need for further research testing whether these strategies improve pulmonary outcomes without an increased risk of impaired neurodevelopmental or other adverse effects. © 2006 Nature Publishing Group. All rights reserved.