In order to assess how bone substitute materials determine bone formation in vivo it is useful to understand the mechanisms of the material surface/tissue interaction on a cellular level. Artificial materials are used in two applications, as biomaterials alone or as a scaffold for osteoblasts in a tissue engineering approach. Recently, many efforts have been undertaken to improve bone regeneration by the use of structured material surfaces.In vitrostudies of bone cell responses to artificial materials are the basic tool to determine these interactions. Surface properties of materials surfaces as well as biophysical constraints at the biomaterial surface are of major importance since thesefeatures will direct the cell responses. Studies on osteoblastlike cell reactivity towards materials will have to focus on the different steps of protein and cell reactions towardsdefined surface properties. The introduction of new techniques allows nowadays the fabrication of materials with ordered surface structures. This paper gives a review of present knowledge on the various stages of osteoblast reactions on material surfaces, focused on basic cell events underin vitroconditions. Special emphasis is given tocellular reactions towards ordered nano-sized topographies.