In sodium profiling, the sodium concentration in the dialysis fluid, instead of being constant, follows a time-dependent profile over the course of a hemodialysis session. The main aim of this manipulation is to avoid osmotic disequilibrium by keeping plasma osmolality in the physiological range. Further advantages of sodium profiling are a reduction in the incidence of muscle cramps, improved sodium removal, and improved vascular stability. Many different profiles have been used by various investigators. However, if sodium profiling is not appropriately conducted, sodium accumulation with resulting augmented thirst, increase of interdialytic weight gain, and hypertension may result. Sodium accumulation may, in fact, explain the reduced intradialytic morbidity reported in some short-term sodium profiling studies. Randomized, double-blind studies meeting strict statistical criteria and providing a careful control to maintain equivalent sodium balances between the compared treatments are difficult to perform and have not yet been published. However, because sodium profiling has potential benefits, provided that sodium balance is carefully controlled, it should nevertheless be regarded as a tool that experienced nephrologists can use for the treatment of patients who experience intolerable side effects during standard dialysis.