Plasticization is a major source of performance reduction in polymeric membranes, where uptake of specific vapour or liquid compounds affects either the space between macromolecular chains and thus free volume or directly initiates the partial depolymerization of the polymeric materials. During membrane separations, solutes or major feed components may induce plasticization of the bulk membrane materials, detrimentally affecting the long-term performance and stability of these membranes. This plasticization effect, inherent to operating with polymeric materials, may nevertheless be adjourned through the smart and selective design of materials via crosslinking, polymer blending, functionalization, grafting, and incorporation of nanomaterial additives into the polymer matrix. This review aims at critically presenting recent and relevant approaches tackling the plasticization of glassy polymeric membranes, which occurs during both gas separation and organic solvent filtration. Recommendations for future work, addressing aspects related to both materials and process engineering are proposed here.