At an implant site, a manmade material meets human tissue, and the manmade material is highly perturbed by the preceeding surgical procedure. The focus of the action, and thus the focus of scientific interest, is the interface between the foreign material and the tissue. The primary interaction occurs on a molecular scale, and involves adsorption and reactions of biomolecules, water and inorganic ions respectively from the bioliquid as well as dissolution of atomic, ionic or molecular fragments from the biomaterial. Successively changing conditions in the tissue, owing to the ongoing healing process and concerted modifications of the surface properties of the biomaterial, make the material-tissue interface a dynamic, non-reversible system in space and time. Secondary processes, induced by the primary processes, may occur far from the interface in the surrounding tissue or as systemic effects. The lack of understanding of the primary processes is a major obstacle in the development of better and new biomaterials and implants. A systematic research approach requires development of sensitive and interpretable biological in vivo and in vitro evaluations procedures, in combination with systematic variation of the surface properties of the biomaterials. The latter can divided into two principally different categories; the surface chemical properties and the surface microarchitecture. These properties can and should be varied independently, but should also be combined in the search for synergistic effects. Modem surface science offers a variety of methods for variation of surface properties ( e.g. physical vapour deposition (PVD) and chemical vapour deposition (CVD) coating techniques, glow discharge plasma treatment) and for their characterisation (surface spectroscopies like X-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), secondary ion mass spectrometry (SIMS), etc.). Surface microarchitecture can similarly be prepared by nano- to micrometer fabrication techniques and analysed by high resolution microscopies (scanning tunneling microscopy (STM), atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM)). The combination of these techniques — biological in vitro and in vivo evaluation methods and surface preparation and characterization — constitutes a necessary framework for a systematic approach in biomaterials research.