Most of the contemporary guidelines on newborn resuscitation are based on experience but lack scientific evidence. The use of 100% oxygen is one of the more evident. Today, these practices are questioned, particularly for the resuscitation of moderately depressed full term or near term newborns. Results of recent meta-analysis of trials that compared ventilation with air versus pure oxygen at birth suggests current practices should be revisited. On the basis of these data, air can be the initial gas to use for these babies. Large scale trials, including preterm and cause and/or severity of initial asphyxia, must now be undertaken before the publication of new guidelines for these populations. Particularly severely asphyxiated infants might require supplemental oxygen with titration of oxygen delivery and continuous monitoring of oxygen saturation.