Cholestasis may result either from a functional defect in bile formation at the level of the hepatocyte or from an impairment in bile secretion and£ ow at the bile duct level1^ 3. Under normal conditions hepatobiliary transport systems mediate hepatic uptake and excretion of bile salts and other biliary constituents such as bilirubin into bile. Transport defects may be hereditary due to genetic defects or acquired as a result of cholestatic injury (eg drugs, hormones, proin£ ammatory cytokines, biliary obstruction or destruction). Reduced expression and function of these transport systems can cause or maintain cholestasis. In addition to these pro-cholestatic changes, recruitment of alternative e¥ ux pumps and induction of phase I and II detoxifying enzymes may limit hepatic accumulation of potentially toxic biliary constituents in cholestasis by providing alternative metabolic and escape routes. These transporter changes are mediated by bile salts, proin£ ammatory cytokines, drugs and hormones at a transcriptional and post-transcriptional level. Alterations of hepatobiliary transporters and enzymes are relevant both for a better understanding of the pathophysiology of cholestasis and as potential targets for pharmacotherapy.