Inborn errors of bile acid synthesis can produce life-threatening cholestatic liver disease (which usually presents in infancy) and progressive neurological disease presenting later in childhood or in adult life. Both types of disease can often be treated very effectively with bile acid replacement therapy and it is therefore important to diagnose these disorders as early as possible. The cholestatic disease in infancy is characterised by conjugated hyperbilirubinaemia with raised transaminases but normal γ-glutamyl transpeptidase and a biopsy showing a giant cell hepatitis. There is usually evidence of fat-soluble vitamin malabsorption. The neurological presentation often includes signs of upper motor neurone damage (spastic paraparesis). The most useful screening test for many of these disorders is analysis of urinary cholanoids (bile acids and bile alcohols); this is usually now achieved by electrospray ionisation tandem mass spectrometry. The disorders that are discussed in this review are: 3β-hydroxysteroid-Δ5-C27-steroid dehydrogenase deficiency, Δ4-3-oxosteroid 5β-reductase deficiency, sterol 27-hydroxylase deficiency (cerberotendinous xanthomatosis, CTX), oxysterol 7α-hydroxylase deficiency (including one form of hereditary spastic paraparesis) and the amidation defects, bile acid-CoA: aminoacid N-acyltransferase (BAAT) deficiency and bile acid-CoA ligase deficiency. The disorders of peroxisome biogenesis and peroxisomal β-oxidation that affect bile acid synthesis will be covered in the review by Ferdinandusse et al.