Despite its potential toxicity, bilirubin may have an important and positive physiologic role (278,561). Bilirubin is a powerful antioxidant in vitro (278) and there is a positive relationship between serum bilirubin levels and antioxidant activity in term and preterm infants (562,563,564). Bilirubin may have a physiologic role as an antioxidant in the human neonate (279,564,565). In sick neonates who have circulatory failure, asphyxia or sepsis, the rate of rise of TSB is less than in control infants (279,565) suggesting that bilirubin is consumed to cope with oxidative stress (561). Because of the possibility that oxidative injury might play a role in the development of retinopathy of prematurity, investigators have evaluated the relationship between bilirubin levels and retinopathy of prematurity (181,181,566,567,568,569 and 570). Of eight published studies, however, six show no protective effect of an elevated TSB level (567,568,569,570,571,572). In adults there is clear evidence that decreased TSB levels are associated with an increased risk of coronary artery disease and peripheral vascular disease (561), but we have yet to identify newborns who have suffered a bad outcome because they have too little bilirubin in their serum.