Over time, functionalized polysulfones have been obtained through various synthetic routes, aiming at the preparation of high-performance materials with targeted functions for specific applications. The successful use of polysulfones and chemically functionalized polysulfones in the fabrication of membranes with applicability in clinical dialyzers, separation of water/organic solvent mixtures, wastewater treatment, gas separation, fuel cells or as a support for composite membranes encourages the study of chemical modification methods of these polymers that lead to the improvement of the properties and the broadening of the applications field. This review summarizes the research progress on the development, investigation, and application of functionalized polysulfones and analyzes why some of their properties, especially surface and morphological ones, should be considered for their extensive use in industrial and environmental scope, membranes for electro-electrodialysis, separation of enantiomer mixtures, ultrafiltration and direct osmosis processes, removal of metals, anion or proton exchange membranes for fuel cells, but also in the biomedical field as hemodialysis membranes, immune response modulators, materials with antimicrobial activity. In addition, the present review highlights the challenges and recent advances achieved through various synthetic approaches that overcome the existing problems and improve the performance of these polymers in medical and industrial fields.