The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was a pioneering study that not only proved that ablative therapy could prevent the late and blinding cicatricial stages of ROP, but also elucidated its natural history.1 As the first study of its kind to apply the newly defined International Classification for ROP to gather data prospectively from serial eye examinations undertaken on 4099 infants at high risk for ROP, the study provided the medical community’s initial understanding of the incidence and early course of ROP. The insights from CRYO-ROP included the following: (1) birth weight (BW) and postmenstrual age are independent and significant predictors of ROP, (2) the severity of ROP is inversely correlated with postmenstrual age and BW, (3) the timing of ROP events are best predicted by postmenstrual rather than chronological age (although severe ROP occurs more frequently in smaller and more immature infants, it takes longer to develop) and (4) the rate of treatment requiring (threshold) ROP in a sample of infants with BWs less than 1251 g was about 6%.