Oxygen supplementation is a risk factor for retinopathy of prematurity (ROP) but is also necessary for the survival of extremely preterm infants. Oxygen supplementation to preterm infants must balance these risks and benefits. Lower oxygen levels promote the vascular development of eyes, lungs, and other organs but are associated with increased mortality rates. Higher oxygen saturation levels are needed for extrauterine adaptation, energy generation, and survival but increase the risk of ROP. To our knowledge, the optimal oxygenation (including optimal oxygen saturation at different postnatal ages) is not known. In this issue of JAMA Ophthalmology, Shukla et al1 begin to address the complexity of optimizing the balance between the risk factors of ROP and mortality rates by examining the association of biphasic vs static oxygen saturation targets with ROP.