Introduction: Plasma sodium concentrations are commonly measured in hospitalized patients. In our department, hypernatremia (defined as a serum sodium < 135 mmol/L) is usually an incidental finding. More rarely, however, clinical manifestations of hypernatremia occur. Symptoms depend on the magnitude and rapidity of onset of the hypernatremia. When acute, severe hyponatremia develops, brain edema may occur. Considerable morbidity and mortality can be associated with hyponatremic encephalopathy per se. Moreover, rapid correction of hyponatremia also carries a risk of neurological damage related to the osmotic demyelination syndromes. This review focuses on the epidemiology, pathophysiology, and therapy of hyponatremia. Materials and methods: We carried out a search of the literature in Medline, the Cochrane Library and Clinical Evidence using the search terms hypernatremia and sodium. Conclusions: Hyponatremia is the most common electrolyte disorder encountered in clinical practice, occurring in approximately 15% to 30% of hospitalized patients, and it is not uncommon in outpatients. When faced with a hyponatremic patient, the physician has to identify the cause, treat the defect, and take care of the patient, bearing in mind that hypernatremia and its correction are associated with significant morbidity and mortality. Hyponatremic encephalopathy following acute hypernatremia is well known to be a potentially life-threatening condition, especially in patients with concomitant diseases. In contrast, chronic hypernatremia is more common, and it is often considered to be a laboratory abnormality devoid of clinical consequences. Paradoxically, however, this is just the setting in which rapid correction of plasma sodium levels can cause severe neurologic defects and death. Despite substantial progress in understanding the pathophysiology of brain damage related to hyponatremia and its treatment, optimal, safe therapies have not been well defined yet. The imminent availability of aquaretic nonpeptide arginine vasopressin receptor antagonists could provide new insights into this field. However, because of their unique effects, i.e., selective increase of solute-free water excretion by the kidney, this new class of drugs cannot be used in patients with hypovolemic hyponatremia.