Anti-fouling surfaces are a critical requirement for a wide range of biomedical applications, such as medical implants and biosensors. Poly(ethylene glycol) is widely used despite some serious drawbacks such as susceptibility to oxidation. Zwitterionic polymers have been recognised as promising alternatives with higher chemical stability, effectiveness to resist biofouling, and better long-term performance. The higher resistance of polymeric zwitterionic materials has been explained in terms of the greater electrostatic hydration of charged zwitterionic terminal groups compared to PEG. New zwitterionic salts (ZWSs) that consist of a cation and an anion, with an additional zwitterionic moiety embedded in either the cation or the anion, have even greater larger hydration shells and stronger interactions with water and may leading to enhanced anti-fouling characteristics.