Intrahepatic cholestasis of pregnancy (ICP) occurs mainly in the third trimester and is characterised by pruritus and elevated serum bile acid levels. ICP is associated with an increased perinatal risk and higher rates of foetal morbidity and mortality. Although the pathogenesis of this disease is unknown, a genetic hypersensitivity to female hormones (oestrogen and/or progesterone) or their metabolites is thought to impair bile secretory function. Recent data suggest that mutations or polymorphisms of genes expressing hepatobiliary transport proteins or their nuclear regulators may contribute to the development and/or severity of ICP. Unidentified environmental factors may also influence pathogenesis of the disease. This review summarises current knowledge on the potential mechanisms involved in ICP at the molecular level.