The majority of newborns is affected by jaundice after birth. While most jaundice is physiologic, severe hyperbilirubinemia can lead to serious complications, such as chronic bilirubin encephalopathy. Hyperbilirubinemia typically results from increased bilirubin production, impaired clearance, excessive reabsorption, or a combination of these factors. Systematic risk assessment and screening are recommended for all infants to prevent neurologic injury from hyperbilirubinemia. Infants born prematurely and those with risk factors for bilirubin neurotoxicity warrant closer monitoring. Phototherapy is usually effective in lowering bilirubin levels, and exchange transfusion is rarely performed.