Because of the high frequency, serious sequelae, and complex and costly management, neonatal jaundice is a good candidate for preventive treatment. In this respect the clinical problem of neonatal jaundice has many similarities with the problem of hemorrhagic disease of the newborn. Both conditions are transient peculiarities of newborn metabolism. Most neonates exhibit the biochemical abnormality, but a small minority is placed in jeopardy of life or suffers serious sequelae. In both conditions a loose relationship exists between the degree of biochemical abnormality and the clinical manifestations that are poorly predicted by monitoring the abnormalities. The administration of vitamin K at birth corrected the biochemical abnormalities and eliminated clinical hemorrhagic disease. The simplicity, efficacy, and safety of vitamin K prevention of hemorrhagic disease of the newborn is the prototype in the search for the solution to the problem of neonatal jaundice. For most neonates, antenatal phenobarbital comes close to this prototype in terms of efficacy and simplicity. The combination of antenatal and postnatal therapy seems suitable for use in preterm labor in combination with tocolysis. This recommendation is conditional on the demonstration of safety by long-term follow-up. The competitive inhibition of HO by synthetic metalloporphyrins offers an even simpler solution, but the level of efficacy achieved with the doses and compounds used so far are not comparable with that of phenobarbital. For the time being, phenobarbital is recommended for population groups with high risk of severe neonatal jaundice, or scarcity of resources for the management of neonatal jaundice with phototherapy and exchange transfusion.