Prerequisites for cell survival include avoidance of excessive cell volume alterations. Cell membranes are highly permeable to water, which follows osmotic gradients. Thus, cell volume constancy requires osmotic equilibrium across cell membranes. Cells accumulate osmotically active organic substances and compensate their osmolarity by lowering cytosolic Cl^– concentrations. Following cell shrinkage, regulatory cell volume increase is accomplished by ion uptake (activation of Na⁺, K⁺, 2Cl^– cotransport, Na⁺/H⁺ exchange in – parallel to Cl^–/HCO3 exchange and Na⁺ channels), by cellular accumulation of organic osmolytes (e.g. myoinositol, betaine, phosphorylcholine, taurine) as well as by proteolysis leading to generation of amino acids and glycogenolysis generating glucose phosphate. Following cell swelling, cell volume is restored by ion exit (activation of K⁺ channels and/ – or anion channels, KCl cotransport, parallel activation of K⁺/H⁺ exchange and Cl^–/HCO3 exchange), release or degradation of organic osmolytes as well as stimulation of protein synthesis and of glycogen synthesis. The activity of cell volume regulatory mechanisms is modified by hormones, transmitters and drugs, which thus influence protein and glycogen metabolism. Moreover, alterations of cell volume modify generation of oxidants and the sensitivity to oxidative stress. Deranged cell volume regulation significantly contributes to the pathophysiology of several disorders such as liver insufficiency, diabetic ketoacidosis, hypercatabolism, ischemia, and fibrosing disease.