The surface is of critical importance in determining the in vivo performance and acceptance of an implant, with respect to both tissue and blood. Material surface properties have been studied intensively, but only in recent years have quantitative, mechanistic links been made to biomolecular and cellular interactions driven by the surface. This review focuses mainly on polymeric surfaces both because of their increasing use as biomaterials, and because of the diversity of biomatrix modifying structural motifs they present. This has allowed valuable new surface structures to be developed both as models for understanding biocompatibility, and for engineering better implant materials in the future. The emphasis in this review is on the relevant ‘chemical biology’ of the material interface.