This article reviews surface grafting of star-shaped PEO. The use of star-shaped polymers is compared to linear PEO chains regarding the layer preparation and the ability of the resulting surfaces to resist protein adsorption. We then focus on the use of end-functionalized, star-shaped, PEO-based prepolymers that are able to form covalent crosslinks and functional polymer networks on the substrate. Examples are given for specific protein adsorption as well as for cell adhesion on such layers by covalent embedding of biofunctional molecules. The possibility of coating biomedically relevant polymer substrates in three-dimensional geometries is discussed and examples are shown for poly(ethylene terephthalate) monofilament constructs.