Background:The world production of whey was estimated to be more than 200 million tons per year. Although whey is an important source of proteins with high nutritional value and biotechnological importance, it is still considered as a by-product of the dairy industry with low economic value due to low industrial exploitation. There are several challenges in the separation of whey proteins: low concentration, the complexity of the material and similar properties (pI, molecular mass) of some proteins.Methods:A narrative review of all the relevant papers on the present methodologies based on ion-exchange and adsorption principles for isolation of whey proteins, known to the authors, was conducted.Results:Traditional ion-exchange techniques are widely used for the separation and purification of the bovine whey proteins. These methodologies, based on the anion or cation chromatographic procedures, as well as combination of aforementioned techniques are still preferential methods for the isolation of the whey proteins on the laboratory scale. However, more recent research on ion exchange membranes for this purpose has been introduced, with promising potential to be applied on the pilot industrial scale. Newly developed methodologies based either on the ion-exchange separation (for example: simulated moving bed chromatography, expanded bed adsorption, magnetic ion exchangers, etc.) or adsorption (for example: adsorption on hydroxyapatite or activated carbon, or molecular imprinting) are promising approaches for scaling up of the whey proteins’ purification processes.Conclusion:Many procedures based on ion exchange are successfully implemented for separation and purification of whey proteins, providing protein preparations of moderate-to-high yield and satisfactory purity. However, the authors anticipate further development of adsorption-based methodologies for separation of whey proteins by targeting the differences in proteins’ structures rather than targeting the differences in molecular masses and pI. The complex composite multilayered matrices, including also inorganic components, are promising materials for simultaneous exploiting of the differences in the masses, pI and structures of whey proteins for the separation.