Significant discordances are observed between the therapeutic needs of patients with end-stage renal disease and the current emphasis in renal science and technologies. These discordances manifest in the observation that renal replacement therapies fail to attenuate the impact of the patient status at the time of initiation of renal replacement on mortality and morbidity; in the failure to apply a rigorous approach for fluid management, despite its technical simplicity; in the inadequacy of dialysis in the correction of deficient excretion of some solutes (phosphate and potassium), and in the greater impact of hormonal replacement on outcome than that observed by dialytic techniques. We suggest that these discordances find their root in the limited spectrum of uremic solute removal that is currently available with various dialytic techniques, and we suggest that a re-examination of the therapeutic targets in dialytic therapy may be needed in order to supercede the therapeutic plateau at which the therapy is currently fixed.