The physiological mechanisms by which aquatic animals regulate the osmoconcentration of their body fluids remain unclear despite many excellent studies of tissue and cell function. This review summarizes the current status of an ongoing molecular biological approach to investigating transporters and transport-related enzymes in ion-transporting gills of osmoregulating crustaceans. We have identified cDNAs coding for six candidate proteins in gills of the blue crab Callinectes sapidus and the green shore crab Carcinus maenas, including a Na K -ATPase α-subunit, a V-type H -ATPase B-subunit, a Na /H exchanger, a Na /K /2Cl⁻ cotransporter, two isoforms of carbonic anhydrase, and arginine kinase. Although our account is far from complete, examination of mRNA abundance by quantitative reverse transcription/polymerase chain reaction (RT/PCR) has identified candidates that are preferentially expressed in gill epithelium, including the Na K -ATPase α-subunit and Na /H exchanger. The osmoregulatory response to salinity reduction includes enhanced mRNA expression of at least one form of carbonic anhydrase.