The present invention provides counter flow cascade separation systems useful to separate solute/solute pairs present in a solvent. The separation systems include a series of interconnected stages with each stage comprising a combination of a diafilter preferentially permeable for one solute and an ultrafilter that accepts a permeate flow from the diafilter. The ultrafilter is permeable to solvent. Solute/solute pairs are preferentially separated by the diafilter into permeate and retentate flows and excess solvent is removed from the permeate flow by the ultrafilter and recycled back into the system. Stages are combined to form a counter flow cascade separation system capable of operation approaching an ideal counter flow cascade.