The association of glucose-6-phosphate dehydrogenase deficiency (G6PD def) with severe neonatal jaundice (NJ) and Kernicterus was described just over 30 years ago in reports from Sardinia (1-4) Singapore (5,6) and Greece (7,8). In this review we will examine the progress made since that time in our understanding of the pathophysiology of severe NJ associated with G6PD def, its global epidemiology, and its role in the balanced polymorphism of the G6PD def gene (Gd). Including this review in the Festschrift to Spyros Doxiadis should highlight his contribution to the field. In Greece the search for a new cause of severe NJ and Kernicterus was triggered by his realization that the recognized at the time, causes of severe NJ were absent in a large proportion of the neonates treated at the "Alexandra" Maternity Hospital in Athens (9).