Today it is essential that we define care practices in neonatology that not only increase survival but also produce optimal pulmonary and neurodevelopmental outcomes for our patients. Assisted ventilatory care continues to be influential at all three levels. In this article, the authors discuss current understanding of the possible mechanisms for pulmonary and neurologic injury, or benefits associated with ventilation at both low and high PaCO2 levels, as well as evidence for neurodevelopmental sequelae with various ventilator strategies.