Nonspecific protein adsorption and/or microbial adsorption on biomedical materials adversely affects the efficacy of a range of biomedical systems, from implants and biosensors to nanoparticles. To address this problem, antibiofouling polymers can be coated on biomedical devices or built into nanoparticles to confer protein and/or microbial repellent properties. The current review provides an overview of the range of synthetic polymers currently used to this end and explores their biomedical potential. The most widely-used antifouling polymer, poly(ethylene glycol) (PEG) is reviewed alongside several promising alternatives, including zwitterionic polymers, poly(hydroxyfunctional acrylates), poly(2-oxazoline)s, poly(vinylpyrrolidone), poly(glycerol), peptides and peptoids. For each material, notable applications for both nanomedicine and macroscopic surface coatings are highlighted.