Numerous materials have been employed in the surface modification of membranes, including different polymers and nanomaterials over the years. The pernicious challenges of membrane separation include the trade-off between water permeability and solute rejection as well as fouling when it is tested under liquid conditions. Zwitterionic polymers have attracted wide interest due to their unique properties of containing both cationic and anionic groups while maintaining electroneutrality and high hydrophilicity. These zwitterionic polymers have been utilized as coating materials or grafted layers not only on the surfaces of porous membranes but also as thin film composite membranes. To illustrate, the membranes modified with this class of materials are capable of resisting foulants through two distinct mechanisms, which are the hydration layer formation and steric repulsion effect, showcasing their unique chemical properties. To bridge the gaps of the recent development of zwitterionic membranes and their relationships with foulants for targeted separation such as ultrafiltration (UF), nanofiltration (NF), and reverse osmosis (RO), this critical review will first fundamentally classify the fouling into four categories according to their characteristics and fouling mechanisms, namely, inorganic foulants, nonmigratory foulants, spreadable foulants, and proliferative foulants. The antifouling strategies which are active antifouling and passive antifouling (e.g., fouling resistance and fouling release) will be summarized. Apart from that, the chemistry, morphology, and modification approaches of zwitterionic membranes including surface coating, surface grafting, and physical blending on targeted applications as well as the separation performance of the state-of-the-art membranes will be presented in detail. Lastly, the summary, outlook of major challenges and opportunities of the zwitterionic materials will be highlighted. It is anticipated that this review can generate a pathway to facilitate the next generation of zwitterionicbased membranes with superior separation performance for specific separation.