An infant's direct (conjugated) serum bilirubin level is 3 mg/dL. The guidelines from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition use the following definition for abnormal direct bilirubin: direct bilirubin is >1 mg/dL if total bilirubin is <5 mg/dL, or direct bilirubin is >20% of the total if the total bilirubin is >5 mg/dL. Conjugated hyperbilirubinemia is never normal or physiologic. It occurs in 1 in every 2500 infants. A persistent or increasing elevated direct bilirubin is always pathologic and must be evaluated promptly. Early diagnosis is urgent and treatment is essential because it means a better outcome for the infant and can be potentially lifesaving (eg, biliary atresia). The goal is to complete the evaluation by 45 to 60 days of age (surgery for biliary atresia has its best outcome if performed before the age of 45–60 days).