Despite the limitation of the few countries and studies covered, this systematic review has shown that a range of maternal and neonatal factors that can be effectively addressed at all levels of health care delivery by available interventions continue to place infants in LMICs at increased risk of severe hyperbilirubinemia. The need for more robust epidemiological studies on the profile of infants with or at risk of severe hyperbilirubinemia across all the eligible LMICs is demonstrated by the findings in this report. The emerging recognition of hemolytic disease in fetus and newborn and other neonatal jaundice as separate and important disease category in the post-2015 global child health agenda offers an unprecedented opportunity to curtail the avoidable burden of severe hyperbilirubinemia, especially in the most developmentally disadvantaged LMICs.