ABSTRACTDuring hemodialysis, blood comes in contact with a large volume of dialysate. Since the purity of dialysate has been linked to acute and long‐term complications in hemodialysis patients, the limit of bacterial and endotoxin contamination has been reduced in recent years. Questions have been raised as to whether ultrapure dialysate is required to prevent such complications; in particular, the chronic inflammatory status frequently found in chronically hemodialyzed patients. In vivo and in vitro data suggest that cytokine stimulation in the blood depends on the concentration of bacteria or endotoxin in the dialysate and on the endotoxin permeability of the dialysis membrane. It is not proven whether ultrapure dialysate reduces significantly proinflammatory cytokine generation compared with standard dialysate within the limits of recent recommendations, if rather impermeable dialysis membranes are used. Cuprophane membranes are more permeable to cytokine‐inducing substances compared with synthetic membranes such as polysulfone and polyamide. Clinical reports have also attempted to link several acute and chronic complications of hemodialysis to dialysate purity. To date, however, there is no large randomized clinical trial demonstrating that ultrapure dialysate significantly reduces biomarkers of inflammation and other consequential putative complications, including dialysis‐related amyloidosis, erythropoietin requirement, and cardiovascular morbidity and mortality. In conclusion, based on the existing clinical data, ultrapure dialysate is recommended in the setting of suboptimal bacteriologic quality of standard dialysate and the use of permeable dialysis membranes.