Knowledge of the complexity of cell-material interactions is essential for the future of biomaterials and tissue engineering, but we are still far from achieving a clear understanding, as illustrated in this review. Many factors of the cellular or the material aspect influence these interactions and must be controlled systematically during experiments. On the material side, it is essential to illustrate surface topography by parameters describing the roughness amplitude as well as the roughness organization, and at the scales pertinent for the cell response, i.e., from the nano-scale to the micro-scale. Authors interested in this field must be careful to develop surfaces or methods systematically, allowing perfect control of the relative influences of surface topography and surface chemistry.