Na+/H+ exchangers (NHE) are plasma transmembrane proteins that exchange extracellular Na+ for intracellular H+. Several isoforms of these antiporters belonging to the same gene family have been cloned and four of them (NHE1 to NHE4) are expressed in the kidney. In the kidney, NHEs isoforms display different tubular and membrane (apical vs basolateral) localization and are involved in different functions: regulation of pH and cell volume, NH4+ secretion and NaHCO3 and NaCl reabsorption. NHE3, which is the apical isoform of the proximal tubule and thick ascending limb of Henle, is involved in bicarbonate reabsorption and displays activation during metabolic acidosis. These recent data showing the acid-activation of NHE3 suggest that NHEs isoforms could be involved in the pathogeny of tubular acidosis.