Cholestasis results from restricted flow of bile due to obstruction or reduced secretion. Neonatal cholestasis is characterized by elevated direct (conjugated) bilirubin (>1-2 mg/dL), and it is present in approximately 1 in 2500 full-term infants. While jaundice due to elevated indirect, or unconjugated, bilirubin is common, jaundice that occurs within the first 24 hours of life or persists past two weeks of age, occurs in formula-fed infants, or results from increased direct/conjugated bilirubin warrants further evaluation and treatment. The most common cause of neonatal cholestasis is biliary atresia, but genetic and/or metabolic disorders are frequent reasons as well. In addition to jaundice, clinical findings may include dark-colored urine, acholic stools, and hepatomegaly. The most common genetic cause of neonatal cholestasis is Alagille syndrome which is characterized by dysmorphic features, cardiac defects, kidney abnormalities, pancreatic insufficiency, and skeletal changes. Other genetic conditions include peroxisome biogenesis disorders (Zellweger syndrome), cystic fibrosis, Smith-Lemli-Opitz syndrome, and a variety of inborn errors of metabolism. In addition to the neonatal period, cholestasis can present at any age from infancy to childhood or adolescence to adulthood. Women with genetic predispositions may present with intrahepatic cholestasis of pregnancy (ICP) as well as with use of oral contraceptives, and these situations may resolve after delivery or discontinuation of oral contraceptives. Symptoms can occur in an episodic manner and include pruritus, jaundice, gallstones, hepatic fibrosis, cirrhosis, and abnormal liver function studies. Conditions including alpha-1-antitrypsin deficiency may increase the risk for adult-onset cholestasis. Severity ranges significantly from a relatively benign but recurrent course to death from end-stage liver disease. Treatments vary depending on the underlying condition and may include laboratory monitoring, medication, cholecystectomy, or liver transplant. The majority of cholestatic conditions are inherited in an autosomal recessive pattern, but a few conditions demonstrate autosomal dominant inheritance.