Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High-sodium bicarbonate-based dialysate was first formulated in 1982 to enable short, safe, comfortable, high-efficiency hemodialysis (HD). Near-universal adaptation of these high-sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patient's serum sodium activity. Then, rather than choosing between comfortable, safe, high-efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low-sodium, high-efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low-efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter- and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20–40% of patients. The application of even more severe salt loading through high-salt sodium modeling only accentuates the long-term problems of excessive thirst, weight gain, and hypertension.