An algorithm is developed for describing ideal membrane cascades for fractionation of binary and pseudo-binary mixtures. It is shown that solvent management plays a key role in determining both purification and yield. Development of efficient diafilters is needed if membrane cascades are to achieve their full potential in competing with both chromatography and simulated moving bed operations in downstream processing of proteins. Such a replacement will also be important for fractionation of higher titers and larger substrates, such as plasmids, viruses, and even whole cells.