This brief overview considers the mechanisms of adaptation of animal cells to anisosmotic media in the framework of a comparative approach. Successful adaptation of animal cells to abrupt changes in the NaCl content of their environment depends on (1) mechanisms of osmolality and volume control and (2) the use of different organic molecules acting as ‘compensatory osmolytes’. Up to now, the importance of this last process has been largely underestimated. It concerns the use of different organic osmolytes, aminocompounds and carbohydrates which can oppose or ‘compensate for’ the disrupting effects that changes in the intracellular level of inorganic ions can have on the organization and activity of different macromolecular structures. Contrarily to the cells of euryhaline invertebrates, most mammalian cells seem to lack the possibility to regulate effectively their content of organic compensatory solutes. Despite the presence of effective mechanisms of cell volume and osmolality control, they thus adapt only with difficulty to abrupt changes in the NaCl level of their environment. An interesting exception is the kidney medulla in which papillary cells seem to control easily the level of some selected amino compounds and carbohydrates. The use of these compensatory osmolytes enables them to cope with the rapid and sometimes important modifications in the NaCl level they are normally withstanding.