The activation of sodium/hydrogen exchanger (NHE) is associated with a variety of cell functions like cell adhesion, migration, proliferation, and apoptosis. Since its discovery, 9 NHE isoforms have been identified, but the most widely spread and the most important for the cellular functions is NHE-1. This ubiquitously expressed sodium/hydrogen exchanger (NHE-1) plays a central housekeeping role in all cells regulating cell volume and internal pH (pHi). At physiological pHi, NHE-1 is essentially inactive but it is extremely sensitive to pHi changes, being rapidly activated by small intracellular hydrogen concentration increases. NHE-1 activity can be stimulated via a series of cell surface receptors, including tyrosine kinase, G-protein-coupled, and integrin receptors. These signals converge, regulating the affinity of the internal hydrogen-binding site. NHE-1 also is a plasma membrane-anchoring protein for the cytoskeleton. Cytoskeleton anchoring of NHE-1 is important for cell adhesion to extracellular matrix proteins and cell migration. Moreover, NHE-1 plays the role of a "scaffold" for the building of various intracellular signaling molecule clusters.