The dialysis prescription can have a substantial impact on the frequency of intradialytic hypotension (IDH). Plasma volume will decline to a greater extent when the ultrafiltration (UF) rate is rapid (high interdialytic weight gains and/or short treatment time), favoring IDH. The relationship of the target weight to the euvolemic weight determines the size of the interstitial fluid compartment, which is a major determinant of the rate of plasma refilling during UF. The higher the dialysate sodium, the smaller the decline in plasma volume for any given amount of UF. Use of a dialysate temperature that prevents a positive thermal balance during dialysis will allow peripheral vascular resistance to be maintained and minimize IDH. A higher ionized calcium during treatment facilitates an increase in cardiac output, a benefit that may be particularly notable in patients with depressed cardiac ejection fraction. Low dialysate magnesium, potassium, and bicarbonate may all favor IDH, although insufficient data are available for definitive conclusions. The choice of antihypertensive medication and the treatment schedule must be carefully considered in patients with IDH. The future integration of technology to monitor blood pressure, plasma volume, and thermal and sodium balance into a computer-based biofeedback system will very likely go a long way toward reducing the frequency of IDH.