Kernicterus occurs in all parts of the world. The risk is increased in countries where glucose-6-phosphate dehydrogenase-deficiency is common. In the 1990's more case reports of infants who developed kernicterus were published than in the previous decades. A combination of reduced concern for jaundice in newborns, early discharge with inadequate follow-up and a decreased awareness of the signs that may herald serious toxicity may have contributed to the apparent increase in the incidence of kernicterus. Although most jaundiced newborns do not need aggressive evaluation or treatment, physicians who deal with such infants still need to be vigilant. We lack the necessary tools to distinguish infants who may be particularly vulnerable to the effects of bilirubin on the brain from those who may tolerate high serum bilirubin levels without harm. Therefore it is imperative that each infant with significant jaundice be conscientiously evaluated and a plan for testing and, if necessary, therapy be formulated. Transcutaneous measurement of bilirubin is a simple tool that significantly reduces the need for invasive tests. Signs of possible neurotoxicity must never be disregarded or neglected. Any jaundiced infant who shows signs of possible neurotoxicity should receive intensive phototherapy as an emergency procedure while further evaluation continues. Further studies regarding bilirubin toxicity and neonatal jaundice are needed, both in the basic science as well as in the clinical arena.