Cholangiocytes possess specific membrane transport systems for a large number of substrates. As a result of the secretion or absorption of solutes, water moves passively across plasma membranes, very likely through water channels; as a result, the volume and composition of primary bile are modified. Cholangiocytes express receptors for secretin and somatostatin, hormones that alter intracellular levels of cAMP in opposite directions; these alterations very likely alter the activation (i.e., phosphorylation state) or number (i.e., by coupled exocytic-endocytic membrane modification) of transporters in the apical or basolateral cholangiocyte membranes. Although our understanding of these mechanisms is sill embryonic, it is anticipated that accelerated research efforts by laboratories utilizing recently available experimental models will provide important advances in the knowledge of the molecular mechanisms involved in the transport of water and solutes by cholangiocytes. The challenge will be to integrate the emerging, often isolated, findings in a physiologically relevant manner to understand how cholangiocytes function normally and in pathological conditions.