The electroneutral cotransport of potassium and chloride is mediated by potassium-chloride transporters, which are encoded by members of the gene family of cation-chloride cotransporters. A significant body of evidence argues for swelling-activated, basolateral potassium-chloride transport in the proximal tubule and thick ascending limb, with a potential role in transepithelial salt transport. However, the lack of specific inhibitors has impeded progress in this area. The cloning of the four potassium-chloride cotransporter genes has sparked new interest in this transport pathway, and promises to yield novel insights into their roles in cellular and renal physiology.