Liver cells possess potent mechanisms to maintain their volume, i.e., their hydration state. These volume-regulatory mechanisms, however, are apparently not designed to maintain absolute cell volume constancy; they rather act as dampeners to prevent excessive cell volume deviations, which would otherwise result from cumulative substrate uptake or anisotonic stress. Furthermore, these volume-regulatory mechanisms can even be activated in the resting state by hormones and other stimuli, and by that means cell volume changes are effected secondarily. Thus, liver cell hydration can change within minutes under the influence of aniso-osmolarity, hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts as an independent and potent signal which modifies hepatocellular metabolism and gene expression. Accordingly, cell volume homeostasis involves the integration of events that allow cell hydration to play a physiologic role as a regulator of cell function.