Sodium is the principal solute in the extracellular compartment and the major component of serum osmolality. In normal persons in the steady state, sodium homeostasis is achieved by a balance between the dietary intake and the urinary output of sodium, whereas in intermittent hemodialysis patients, sodium balance depends on dietary intake and sodium removal during hemodialysis. Thus, the main goal of hemodialysis is to remove precisely the amount of sodium that has accumulated during the interdialytic period. Sodium removal during hemodialysis occurs via convective (~78%) and diffusive losses (~22%) between dialysate and plasma sodium concentration. The latter (the sodium gradient) is an important factor in the 'fine tuning' of sodium balance during intermittent hemodialysis. Most use fixed dialysate sodium concentrations, but each patient has his/her own plasma sodium concentrations pre-hemodialysis, which are quite reproducible and stable in the long-term. Thus, in many patients, a fixed dialysate sodium concentration will cause a persistent positive sodium balance during dialysis, which could possibly cause increased thirst, interdialytic weight gain, and mortality. Several methods will be discussed to reduce positive sodium balance, including sodium alignment.