A wide range of cholestatic liver diseases result from various primary defects in bile formation. Clinical features include jaundice, pruritus, failure to thrive, fat malabsorption, cholelithiasis, and variably progressive cirrhosis. Accurate diagnosis of these disorders is essential for determination of prognosis and selection of the most appropriate therapies. Severe genetic defects in canalicular bile acid and phospholipid excretion lead to progressive liver disease that often requires liver transplantation. Defects in bile acid biosynthesis and aminophospholipid transport may be responsive to medical or non-transplant surgical approaches.