Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For rapid adjustment of cell volume cells release or accumulate ions through respective channels and transport systems across the cell membrane. The most widely used mechanisms of cell volume regulatory ion release include ion channels and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+, K+, 2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is accomplished by the formation or accumulation of organic osmolytes, molecules specifically designed to create intracellular osmolarity without interfering with cellular function. The most widely occurring osmolytes are sorbitol, inositol, glycerophosphorylcholine, betaine, taurine, and amino acids. The osmolytes are either synthesized by or transported into shrunken cells. During cell swelling osmolytes can be rapidly degraded or released. Any given cell may utilize several volume-regulatory mechanisms. Moreover, different mechanisms are utilized in different tissues. The diversity of cell volume regulatory mechanisms allows the cells to defend the constancy of cell volume against a myriad of challenges with relatively little impairment of cellular function.