Diffusion and convection are the main mechanisms involved in the membrane separation processes occurring in extracorporeal hemodialysis. Operational parameters should be optimized in hollow fiber hemodialyzers to achieve the maximal efficiency. The nature of blood which is a non Newtonian fluid, requires specific attention in the design of dialyzers to ensure that the blood compartment operates properly. Similar attention must be placed in the design of the dialysate compartment to ensure a homogeneous distribution of the fluid and to prevent blood to dialysate flow mismatch. Finally, the membrane represents the third component of the hemodialyzer. Membrane performance depends on the used biomaterial, its biocompatibility, the thickness, the hydrophilic-hydrophobic mixture, the hydraulic permeability and the number and diameter of the pores. In this setting, diffusion and convection tend to reciprocally interfere, producing a final result that depends on the prevalence of one or the other mechanism for every specific solute.