Among many substances accumulated or generated by renal failure, much attention has focused on the pathogenetic effects of advanced glycation end-product (AGE)-bound proteins such as AGE-modified beta 2-microglobulin, and bioactive substances such as inflammatory cytokines. In order to remove these substances efficiently, dialysis membranes in the year 2000 should have a higher molecular cut-off point and a sharper cut-off curve, with less formation of concentration polarization, or a greater adsorbing capacity for target substances with less ensuing protein gel layer. Adequate supplementations for depleted substances by more efficient dialysis will be necessary as at present with carnitine and vitamins. Further, from now until the year 2000, membranes in which biocompatibility nearly corresponds to that of capillary endothelium, and safe and economical purification systems of dialysate should be realized.