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New evidence is emerging to address the continued uncertainty regarding the optimal range to target oxygen saturation levels in preterm infants.A recently published systematic review summarized the existing evidence for currently used oxygen saturation targets in preterm infants and highlighted the paucity of randomized trials addressing this topic. It appears that higher oxygen saturation levels increase the risk of severe retinopathy of prematurity and pulmonary morbidities. However, data regarding the effects of various target ranges on early mortality and long-term neurodevelopmental outcomes are lacking. A collaborative group of investigators from five independent randomized trials was established to answer this question definitively. Although the final analysis will not be available until 2014, interim results from four of these trials revealed an increase in early mortality when the lower oxygen saturation range is targeted. At present, it may be prudent not to target oxygen saturation levels below 90%. Whatever the optimal range, consistently maintaining the newborn's oxygen saturation levels within target proves an additional challenge for providers. Both technological advancements and optimized patient--caregiver ratios may be useful in achieving targeted oxygen saturation goals.Defining and maintaining optimal oxygen saturations in preterm infants remains a challenge for clinicians caring for preterm infants. However, ongoing investigative collaborations may soon provide guidance.