Abstract   Onset and correction of hypernatraemia constitute major hypertonic stresses for mammalian cells. Cells respond by activating specific osmoregulatory mechanisms allowing to preserve their volume and to adapt to their new environmental conditions. These processes have major implications in the management of hypernatraemia. In particular, cells chronically exposed to hypertonic conditions progressively accumulate organic osmolytes to maintain optimal intracellular electrolyte concentrations. During treatment of hypernatraemia, elevated intracellular organic osmotic content exposes cells to cellular oedema if sodium concentrations are rapidly corrected. In addition, circulating ions equilibrate slowly across the blood-brain barrier during acute changes in plasma osmolality. This can generate major brain water shifts and severe cerebral lesions related to brain shrinking or cerebral oedema.