Maintenance of extracellular fluid volume balance is an essential role of chronic maintenance hemodialysis (HD). In this population, this balance is determined by salt intake during the interdialytic period and sodium removal in HD sessions. Most of the sodium in a HD session is removed by ultrafiltration of plasma water, and the diffusion process becomes responsible for the fine tuning of sodium balance. The observation of little variation in pre-HD serum sodium denotes that HD patients have an individual, stable osmolar set point. A positive dialysate-to-plasma sodium gradient is associated with increased thirst, interdialytic weight gain, and hypertension. To achieve an isonatric HD session, dialysate sodium concentration should approximately match patient’s serum sodium, and all sodium gained in the interdialytic period must be removed by convection. The pre-HD serum sodium concentration may be used as a reference for dialysate sodium prescription in chronic HD. In this article, we also discuss new aspects of sodium balance, with particular attention to new observations on nonosmolar interstitial sodium storage.