Kernicterus in sick and preterm infants is a rarity. Universal availability of phototherapy and concerted clinical efforts to identify, effectively manage and establish clinical guidelines have been instrumental in preventing kernicterus in US intensive care nurseries. However, in sick and preterm infants the absence of precise data on prevalence of bilirubin induced neurologic injury, the lack of proven predictive indices and the absence of evidence-based studies that clearly demonstrate the actual risk of kernicterus. These leave questions regarding the basis for clinical strategies and recommendations for the management of neonatal jaundice in this select population. This article reviews 6 preterm infants selected from the Pilot Kernicterus Registry who had recovered from life-threatening neonatal illnesses, briefly discusses current indices used to ascertain risk, and offers an initial bilirubin level based identification of infants while future directions and studies are conducted to supplement our presently incomplete knowledge for safer clinical practice.