OBJECTIVE The management of jaundice in the newborn infant is an area of clinical practice sorely lacking an evidence-based foundation, and neonatal bilirubin neurotoxicity (kernicterus) continues to occur worldwide. RESULTS Studies suggest that measuring serum or plasma bilirubin binding, in particular the nonalbumin-bound or unbound bilirubin concentration (Bf), would improve jaundice management as it better predicts bilirubin neurotoxicity than the conventionally used total bilirubin concentration (BT). However, many misconceptions persist regarding the relationships between BT, Bf, the magnitude and distribution of the neonatal bilirubin load, and the risk of bilirubin neurotoxicity. CONCLUSIONS Overcoming these misconceptions and integrating Bf and BT into the management of neonatal jaundice may help move clinical practice from its tradition-based approach centered primarily on BT toward an evidence-based approach that will substantially improve our ability to predict bilirubin neurotoxicity and improve the clinical management of this generally benign, but potentially catastrophic, newborn condition.