Retinopathy of prematurity is on the rise and a third epidemic has been identified. In spite of extensive research and progress in the understanding of this disease in recent years, 50 000 children worldwide are blinded by this condition each year. The relation between hyperoxia, low-gestational age, growth retardation, oxygen dependent growth factors, and oxidative stress are now being understood more clearly. We know that in the first phase of retinopathy of prematurity, hyperoxia inhibits vascular endothelial growth factor. In the second phase, vascular endothelial growth factor rises, and when insulin-like growth factor-1 reaches a threshold around 32 to 34 weeks postconceptional age, uncontrolled neovascularization may occur. It is not known whether this new knowledge will have implications for future therapy. However, by strictly avoiding hyperoxia, that is, SaO2>92-93% and avoiding fluctuations in SaO2, it is possible to control and prevent severe retinopathy of prematurity in most cases.