Oxygen was discovered more than 200 years ago and was thought to be both essential and beneficial for all animal life. Although it is now over 100 years since oxygen was first shown to damage biological tissues exposed to high concentrations, and more than 50 years since it was implicated in the aetiology of retinopathy of prematurity, the use of 100% oxygen was still recommended for the resuscitation of all babies at birth as recently as 2000. However, the 2005 International Liaison Committee on Resuscitation (ILCOR) recommendations allow for the initiation of resuscitation with concentrations of oxygen between 21 and 100%. There are strong arguments in favour of a radical curtailment of the use of oxygen in resuscitation at birth, and for devoting resources to defining the margins of safety for its use in the neonatal period in general.