Currently, more than a million patients worldwide are supporting renal function by dialysis as a treatment of choice in the End-stage Renal Disease. Hemodialysis is one of the modalities of renal replacement therapy. Hemodialysis removes nitrogenous and other waste products, corrects electrolyte, water and acid abnormalities by diffusion, convection and ultrafiltration. Hemodialiysis membranes which are presently in use are the synthetic membranes of high biocompatibility (low-flux for conventional hemodialysis and high-flux for hemodiafiltration). Dialysate is a solution of purified water and electrolytes and is used for balancing a composition of blood. Hemodiafiltration is hemodialysis modality that combines principles of hemodialysis and hemofiltration (diffusion and convection) to enhance removal of both, high and low molecular weight uremic toxins. Online hemodiafiltration (OLHDF) offers production of substitution fluid in dialysis machine from fresh dialysate, that’s why the technique of OLHDF is simplified to use and economically acceptable. There are many clinical advantages of OLHDF, some of them are: lower mortality risk, higher delivered dialysis dose, correction of malnutrition, anti-inflammatory effect, improvement of blood pressure and hemodynamic stability, better control of hyperphosphatemia, anemia and greater biocompatibility. Despite of numerous clinical advantages, OLHDF is not still widely in use in maintenance hemodialysis patients, mainly because of the higher price of high permeable filters. Although, any dialysis modality, regardless of performance and efficiency will only partially restore integrity of renal function, OLHDF seems to offer the most physiological way to enhance the removal of uremic toxins and improvement of many comorbidities that are renal patients faced with. OLHDF is a step forward to gold standard in renal replacement treatment.