Kernicterus, or “bilirubin encephalopathy,” is a deposition of indirect bilirubin pigment in basal brain structures (hippocampus, globus pallidus, and other structures), associated with severe hemolytic disease of the fetus/newborn (classically due to HDFN caused by anti-D) or any other clinical situation resulting in severe indirect hyperbilirubinemia. Circulating antigen-positive fetal and/or neonatal red blood cells are destroyed by the maternal antibody, with a resultant increase in indirect bilirubin. This substance, a hemoglobin breakdown product, is lipid-soluble and can cross the blood-brain barrier and deposit itself in the basal brain structures, while direct bilirubin generally does not enter the brain. Traditionally, indirect bilirubin levels above 20 mg/dL were associated with increased risk for kernicterus, but the critical number varies by the age and health status of the child. If bilirubin deposits in the brain structures, the baby may have hypotonia (appear “floppy”), severe lethargy, poor feeding, and a high-pitched cry. The outlook is poor, unfortunately.