Neonatal jaundice is common and usually not concerning when it is secondary to unconjugated hyperbilirubinemia, below the neurotoxic level, and resolves early. Primary care providers should be vigilant, however, about evaluating infants in whom jaundice presents early, is prolonged beyond 2 weeks of life, or presents at high levels. Even in well-appearing infants, fractionated (direct and indirect) bilirubin levels should be obtained in these clinical scenarios to evaluate for potential cholestasis. This review presents an approach to the evaluation of a jaundiced infant and discusses diagnosis and management of several causes of neonatal cholestasis.