The function of the gallbladder is not only to store bile, but also to concentrate it during the interdigestive phase by means of salt-dependent water reabsorption. On the contrary, secretions of water and salt take place during the digestive phase. Dysregulation of ion absorption or secretion are common in many gallbladder diseases, such as colelithiasis. Transepithelial absorptions are determined by the Na+/K+ pump on the basolateral membrane, and by several apical membrane Na(+)-coupled transporters. Among these, some isoforms of Na+/H+ and Cl-/HCO3(-) exchangers have been studied. The presence of a Na(+)-Cl(-) simport has been molecularly and functionally characterized in some animal species. The ion transepithelial secretion is mainly dependent on an apical chloride transport attributable to a CFTR-like cAMP-activated channel with high permeability to HCO3(-). The apical membrane electrical potential is one of the factors influencing anion secretion and is maintained by the activity of cAMP-dependent K+ channels. The regulation of the activity of these channels is complex, because of their sensitivity to voltage, and to intracellular calcium and pH. The coordinated interplay underlying the regulation of transporters and channels needs to be clarified yet, as well as the interactions between transporters, channels and aquaporins.