Cell-substratum interaction is influenced by topographical in addition to chemical cues. The majority of patterning studies on cellular response have been conducted on micropatterned surfaces. Cells clearly respond to the topography of substrates in the micron range in terms of adhesion, proliferation, migration, and gene expression. However, cells in their natural environment also interact with extracellular matrix components in the nanometer scale. This review will cover recent studies that show mammalian cells responding to nanoscale features on a synthetic surface. An important and exciting direction of research in nanomedicine would be to gain a better understanding of the interaction between cells and nanostructures. This will facilitate the creation of the next generation of biomaterials with well-defined nanotopography that can elicit the desired cellular and tissue response.