Hemodiafiltration is the dialytic strategy enabling the high potential of hydraulic and solute permeability of synthetic membranes to be most properly exploited, thus greatly enhancing removal of small and middle-molecular toxic compounds. Several of those solutes have a pathogenic role or are recognized as marker of the most frequent long-term complications and causes of death in HD patients, such as dialysis related amyloidosis, cardio-vascular disease, secondary hyperparatyroidism, inflammation and malnutrition. Improved survival in dialysis has been associated, in observational studies, with the use of high-flux membranes and hemodiafiltration with high volume exchange. On-line production of unlimited amount of sterile dialysate at low cost has favored its extensive diffusion in the recent years, and optimal biocompatibility of synthetic high-flux membranes and the quality of the ultrapure dialysate have contributed to the promising results of the technique. However, to optimize its clinical application and achieve safely the most efficient convective transport, knowledge is required of dialysis systems, dialyzer characteristics and performances, and of the complex interactions between patient and membrane. New hemodiafiltration techniques have been proposed in these years with the aim to improve the efficiency and safety of the technique. More generally, technical aspects and requirements, and experimental and clinical results of the convective-mixed treatments are examined here.