Chloride/bicarbonate exchange activity is present or elicitable in nearly all tissues and cultured cells, where it contributes to the maintenance of cellular proton, chloride and volume homeostasis. The best characterized chloride/bicarbonate exchange protein, red cell band 3 (AE1), is the prototype member of the AE anion exchanger gene family. This gene family includes, in addition to AE1, the related genes AE2 and AE3. These genes and their protein products are expressed in many nonerythroid tissues, and their regulatory properties are under active investigation. Following an introduction which places chloride/bicarbonate exchange in the perspective of cellular pH and volume regulation, this review first will summarize current knowledge of the molecular biology and the molecular genetics of the AE gene family. The second part will describe the results of functional studies of recombinant AE protein expression. The last part will summarize data on endogenous AE protein immunolocalization and regulation.