Cell organization, proliferation, and differentiation are impacted by diverse cues present in the cellular microenvironment. As a result, the surface of a material plays an important role in cellular function. Synthetic surfaces may be augmented by physical as well as chemical means. In particular, patterning and interfacial gradients may be utilized to mitigate the cellular response. Patterning is advantageous as it affords control over a range of feature sizes from several nanometers to millimeters. Gradients exist in vivo, for instance in stem cell niches, and the ability to create interfacial gradients in vitro can provide valuable insights into the influence of a series of minute surface changes on a single sample. This review focuses on fabrication methods for generating micro- and nanoscale surface patterns as well as interfacial gradients, the impact of these surface modifications on the cellular response, and the advantages and challenges of these surfaces in in vitro applications. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys., 2013 51, 775-794