Mechanical ventilation is necessary and life saving in many neonates. Most complications are inherent to this intervention and cannot be confused with iatrogenic errors in judgment or care practices by clinicians. Clinical data suggest that complications such as volutrauma and air leak syndromes can negatively affect long-term pulmonary and non-pulmonary outcomes. Careful attention to many aspects of neonatal care, such as delivery room resuscitation, ventilatory support, and routine care practices, is needed to decrease pulmonary complications of mechanical ventilation. Clinical research is needed to improve mechanical ventilator strategies to reduce pulmonary complications and improve long-term outcomes. © 2008 Elsevier Inc. All rights reserved.