International guidelines for newborn resuscitation recommend the use of 100% oxygen. However, high concentrations of oxygen after asphyxiation activate reactive oxygen species that may contribute to a number of morbidities. Animal models have been useful in describing their mechanisms, but only large-scale clinical trials can provide evidence that may be used to alter clinical practice. It has been demonstrated that neonates recover faster when resuscitated with room air as opposed to pure oxygen and neonatal mortality rates are improved. Increases in saturation are equal with oxygen and room air resuscitation. Studies of normal oxygen saturation immediately after birth suggest that clinicians may unnecessarily be rushing to high saturations. In the first weeks of life, lower saturation targets in preterm infants reduce retinopathy of prematurity and pulmonary complications and may improve growth. The neonatologist would be well served to think of oxygen as a medication, and use it sparingly.