The disorders of the sodium concentration [Na+] are body fluid osmolality disorders called dysnatremias. Clinical chemistry measurements are obtained from blood plasma, part of the extracellular fluid (ECF), where Na+ and accompanying anions that maintain electroneutrality are the dominant osmoles. Since water is highly permeable to nearly all plasma membranes, and body water is regulated to maintain osmolality, it is the amount of the major ECF cation, Na+, and its associated anions that determines the ECF volume. The amount of the major intracellular fluid (ICF) cation, K+, with its associated anions, determines the volume of the ICF. Thus, accounting for anions that maintain electroneutrality in each compartment, the osmolality of each fluid compartment of the total body water (TBW) is equal to that of TBW itself: \( \mathrm{Osm}=2\left[\mathrm{ECF}\ {\mathrm{Na}}^{+}+\mathrm{ICF}\ {\mathrm{K}}^{+}\right]/\mathrm{TBW}. \) Osmolality is a concentration of milliosmoles or millimoles per kg of total body water (TBW). Osmolarity differs in that the concentration is the amount of millimoles per liter of total body water. Since the major body water solutes, in molar quantities, are the charged species Na+ and K+, and their counter anions, millimoles can be approximated as milliequivalents (meq) such that mOsm ~ 2 × total meq of Na+ and K+ per liter of TBW. In this chapter, the terms for osmolarity and osmolality are used interchangeably as mOsm. Since the interface of body fluid compartments occurs at the semipermeable capillary membranes [plasma to interstitial fluid, (P to ISF)], and ISF to intracellular fluid (ICF) cellular plasma membranes, become a barrier for maintaining cell content. The mechanisms evolved to regulate the osmolality of body fluids are largely osmotic forces and accordingly the control of intake and excretion of water. Abrupt changes in ECF [Na+] and osmolality relative to the ICF osmolality cause fluid shifts between ECF and ICF that lead to cellular swelling (hyponatremia) or shrinkage (hypernatremia). Brain cell shrinkage and cerebral edema may lead to neurological deficits and are therefore the most clinically relevant findings. The symptoms are most pronounced in acute cases of the dysnatremias, before cellular volume has adapted or recovered. When plasma osmolality remains high or low for more than 1–2 days, the condition is considered chronic, meaning that enough time has elapsed for recovery of the normal cell volume despite a persistent change in body fluid osmolality. Brain tissue adapts by a process of cell volume decrease or increase to allow for cells to return to normal volume. Dysnatremias are often multifactorial, and clinical evaluation should include evaluation of the volume status as well as concentration measurements. Estimated deficits or excesses need to be determined and osmotic changes need to be corrected at an appropriate rate for the chronicity, based on evidence and best practice guidelines. An estimate of ongoing losses need be calculated and replaced if they would otherwise result in deficits or surfeits. Therefore, measurements of the rate of volumes of fluid coming in and being lost need be made. This includes estimation of insensible losses and interpretation of exiting urine osmotic concentrations. Calculations of electrolyte-free water clearance are recommended to distinguish between isotonic and water components of the total urine volume. Once the diagnosis and corrective therapy has been established and initiated, the underlying disease should be addressed.