Cells of marine species are known to establish osmotic balance with their environment by adjusting the concentrations of organic osmolytes rather than inorganic osmolytes such as sodium, potassium, and chloride. These organic osmolytes fall into three classes: polyhydric alcohols such as sorbitol, amino acids and amino acid derivatives, and urea and trimethylamines. Substantial evidence is available for a central role of each of these classes in osmoregulation in marine species. In this chapter information on the importance of organic osmolytes is extended to a study of isolated mammalian kidney cells. The intracellular concentration of organic osmolytes in these cells responds dramatically to changes in the osmotic environment. The release of sorbitol following hypoosmotic exposure appears to be triggered by calcium, possibly via a mechanism involving membrane recycling. The summarized experiments provide a basis for further work in marine species.