Modern approaches to biomaterials aim to instigate a specific tissue response to create truly biocompatible materials. With this in mind, the responses of cells to biomimetic surface topographies have been studied. This review compares the findings and links the results to the processes which occur when cells contact a surface. Topographical features such as grooves and ridges or pits and pillars can have a dramatic effect on the composition of protein layers affecting protein orientation and conformation. It has been demonstrated that these surface properties along with others, such as surface compliance, can significantly impact on specific cell–surface interactions. Design strategies to minimize foreign body reactions should consider the shape, size, spacing and curvature of topographical features. In doing this, it should be possible to control the signals that are relayed to the nucleus and thus gain a degree of control over the cell behavior and ultimately the tissue response.