Five widely documented mechanisms for chloride transport across biological membranes are known: anion-coupled antiport, Na+ and H+-coupled symport, Cl− channels and an electrochemical coupling process. These transport processes for chloride are either secondarily active or are driven by the electrochemical gradient for chloride. Until recently, the evidence in favour of a primary active transport mechanism for chloride has been inconclusive despite numerous reports of cellular Cl−-stimulated ATPases coexisting, in the same tissue, with uphill ATP-dependent chloride transport. Cl−-stimulated ATPase activity is a ubiquitous property of practically all cells with the major location being of mitochondrial origin. It also appears that plasma membranes are sites of Cl−-stimulated ATPase pump activity. Recent studies of Cl−-stimulated ATPase activity and ATP-dependent chloride transport in the same plasma membrane system, including liposomes, strongly suggest a mediation by the ATPase in the net movement of chloride up its electrochemical gradient across the plasma membrane structure. Contemporary evidence points to the existence of Cl−-ATPase pumps; however, these primary active transporters exist as either P-, F- or V-type ATPase pumps depending upon the tissue under study.