As recently as the year 2000, 100% oxygen was recommended to begin resuscitation of depressed newborns in the delivery room. However, the most recent recommendations of the International Liaison Committee on Resuscitation counsel the prudent use of oxygen during resuscitation. In term and preterm infants, oxygen therapy should be guided by pulse oximetry that follows the interquartile range of preductal saturations of healthy term babies after vaginal birth at sea level. This article reviews the literature in this context, which supports the radical but judicious curtailment of the use of oxygen in resuscitation at birth.