The last decades of bilirubin research seem to have clarified the basic mechanisms by which bilirubin enters the brain. Clinical studies have so far failed to show any value of the presently known risk factors in predicting bilirubin toxicity in the newborn infant, however. This indicates that bilirubin entry into the brain does not necessarily equal bilirubin toxicity. Future research must therefore concentrate on further clarifying the molecular basis for the interaction between the nerve cell membrane and bilirubin as well as bilirubin effects on nerve cell metabolism. Such studies may eventually form the basis for a more rational prophylaxis and a more specific therapy than that which is currently being employed.