Polybetaines, that have moieties bearing both cationic (quaternary ammonium group) and anionic groups (carboxylate, sulfonate, phosphate/phosphinate/phosphonate groups) situated in the same structural unit represent an important class of smart polymers with unique and specific properties, belonging to the family of zwitterionic materials. According to the anionic groups, polybetaines can be divided into three major classes: poly(carboxybetaines), poly(sulfobetaines) and poly(phosphobetaines). The structural diversity of polybetaines and their special properties such as, antifouling, antimicrobial, strong hydration properties and good biocompatibility lead to their use in nanotechnology, biological and medical fields, water remediation, hydrometallurgy and the oil industry. In this review we aimed to highlight the recent developments achieved in the field of biomedical applications of polybetaines such as: antifouling, antimicrobial and implant coatings, wound healing and drug delivery systems.