There is evidence that cellular hydration state is an important factor controlling cellular protein turnover; protein synthesis and protein degradation are affected in opposite directions by cell swelling and shrinking. An increase in cellular hydration (swelling) acts as an anabolic proliferative signal, whereas cell shrinkage is catabolic and antiproliferative. The cellular hydration state is mainly determined by the activity of ion and substrate transport systems in the plasma membrane. Hormones, substrates, and oxidative stress can change the cellular hydration state within minutes, thereby affecting protein turnover. We postulate that a decrease in cellular hydration in liver and skeletal muscle triggers the protein catabolic states that accompany various diseases.