Zwitterionic materials are the latest generation of materials for nonfouling interfaces and membranes. They outperform poly(ethylene glycol) derivatives because they form tighter bonds with water molecules and can trap more water molecules. This feature article summarizes our laboratory's fundamental developments related to the functionalization of interfaces and membranes using zwitterionic materials. Our molecular designs of zwitterionic polymers and copolymers, sulfobetaine-based, carboxybetaine-based, or phosphobetaine-based, are first reviewed. Then, the strategies used to functionalize surfaces/membranes by coating, grafting onto, grafting from, or in situ modification are examined and discussed, and the third part of this article shifts the focus to key applications of zwitterionic materials. Finally, some potential future directions for molecular designs, functionalization processes, and applications are presented.