© Springer-Verlag Berlin Heidelberg 2015. Two decades ago, a consensus of experts on mechanical ventilation indicated that one of the potential strategies to reduce lung injury was to modify blood-gas targets to accept a higher-than-normal PaCO2(Slutsky 1993). This approach to ventilator support has been called permissive hypercapnia, also termed controlled mechanical hypoventilation. In the past, many clinicians aimed to achieve PaCO2levels of 40 mmHg or less in ventilated neonates. Experimental and clinical researches during the last two decades indicate that slightly higher PaCO2levels may allow a reduction in ventilatory support and may reduce the risk for lung injury.