Both secretion and absorption of NaC1 are basic functions of epithelial cells. These transport processes require polarized insertion of proteins specialized in ion transport to either the luminal or the basolateral membranes of epithelial cells. In order to effectively transport NaC1 from the apical to the basolateral side, or vice versa, the task of all participating membrane proteins has to be coordinated. This is achieved by the parallel or, in case of voltage and volume activated channels and transportes, sequential activation of ion channels, membrane transporters and pumps through changes of intracellular ion concentrations, as well as by common intracellular second messenger pathways. In this respect, crosstalk between the basolateral and luminal membranes of epithelia has become an important issue in the understanding transepithelial NaC1 transport [127, 130, 318]. As an additional mechanism to synchronize the various membrane proteins involved in ion transport, a direct interaction of the contributing proteins may play an essential role. In this respect, it has become apparent in recent years that also the cystic fibrosis transmembrane conductance regulator (CFTR) protein could play an important role in directing epithelial NaC1 transport. Defects of CFTR, as they occur in cystic fibrosis (CF), lead to a disturbed NaC1 and water balance. Apparently, this is caused not exclusively by a defect in the cAMP regulated C1-conductance, but also by a lack of regulation of other epithelial membrane conductances. Thus, CFTR truly deserves the name given initially, namely" transmembrane conductance regulator". The present review summarizes current evidence indicating that CFTR in fact is a regulator of membrane conductances and thus is a regulator of NaC1 and fluid transport.