How to control cell behavior at cell-biomaterial interfaces is a critical task in today`s implant science, tissue engineering, and regenerative medicine. Various biomaterial surface modification techniques, either chemical or topographical, have been introduced to induce optimal regulation of cell behavior. Among them, topographic control of cell behavior has long been recognized, for example, cells align to the anisotropic direction of ridge and groove topographies(contact guidance). In this review, cell sensing and response to substratum surface topographies will be reviewed in terms of anisotropic vs. isotropic topographies and microscale vs. nanoscale topographies. It is clear that anisotropic topographies induce morphological cell reaction(cell orientation) and then downstream cell responses. On the other hand, isotropic topographies do not induce contact guidance while influencing collective cell functions(such as degree of adhesion, proliferation rate, degree of differentiation, etc). For both topographies, there exist threshold topographic scales from which specific cell sensing and response occur. Clear understanding of cell response to substrate topographies would be very helpful for developing novel regenerative medicine protocols.