Many of the morbid conditions associated with extreme immaturity are potentiated by an excess of free radicals occurring in infants who developmentally have decreased levels of antioxidants. The optimal oxygen saturation values for the resuscitation, stabilization, and ongoing care of the very low birth weight infant remain largely undefined. We have reviewed the currently available evidence for clinical oxygen use in the newborn period. Until the results of further studies are available, a reasonable approach to resuscitation would include initial resuscitation with 30-40% oxygen for very preterm infants using targeted SpO2 values and blended oxygen during the first 10 min. For ongoing management of preterm infants, SpO2 targets of 85-93% seem to be most appropriate, with alarm limits set within 1 to 2% of these targets with intermittent audits to ensure compliance. There is no strong evidence to support the use of altered limits for the infant who develops early evidence of retinopathy of prematurity. Further prospective studies are required to evaluate the effects of varied oxygen targets on long-term outcome.