Tissue attachment to substratum surfaces is of central importance to the in vivo performance of prosthetic implant materials. It is not yet understood why connective tissue does not attach to the surface of silicone or any other polymeric material. Recently the authors have conclusively demonstrated that micro-range surface roughness modifies cellular responses in cell culture and modifies biocompatibility and tissue attachment in vivo significantly. In order to better understand the basic interactions between living cells or tissues on one hand and man-made substratum surfaces on the other hand, the germane literature is reviewed here. Cells adhere to substratum surfaces mainly through focal adhesions which are a complex of intracellular transmembrane and extracellular proteins. Adhesion is facilitated and modified by proteins adsorbed to the substratum surface. Protein adsorption in turn is modified by the underlying substratum surface properties including surface chemistry, charge, and free energy. When silicone and other polymeric implants having well-defined surface topographic features including pores, pillars, or grooves were implanted, the tissue response to these implants was strongly influenced by the dimensions of these features as well as by other geometric details. Highest biocompatibility along with tissue attachment was seen when topographic features had dimensions of 1-3 microns and a uniform distribution. Cell culture studies revealed that topographic features affect cellular alignment, direction of proliferation, cellular attachment, growth rate, metabolism, and cytoskeletal arrangement. Since discontinuities or curvatures associated with topographic features may represent local changes in surface free energy, it is hypothesized that these discontinuities trigger changes in protein adsorption, protein configuration, and cellular response.