The role of middle molecular weight uremic toxins in the pathogenesis of many co-morbid conditions associated with end-stage renal disease is increasingly recognized. Hence, the hypothesis that their enhanced removal could convey a better survival has been proposed. Actually, HDF is the most effective modality in terms of solute removal, because solute transport is achieved by both diffusion (especially for small molecules) and convection (the most important clearance route for middle molecules). Although some convective transport can be achieved with high-flux HD, only in HDF can the amount of filtered volume reach values of 20 liters per session or more.