Tissue engineering approaches that combine biomaterial-based scaffolds with protein delivery systems have provided a potential strategy for improved regeneration of damaged tissue. The success of polymeric scaffolds is determined by the response it elicits from the surrounding biological environment. This response is governed, to a large extent, by the surface properties of the scaffold. Surfaces of polymeric scaffolds have a significant effect on protein and cell attachment. Multiple approaches have been developed to provide micrometer to nanometer scale alterations in surface architecture of scaffolds to enable improved protein and cell interactions. Chemical modification of polymeric scaffold surfaces is one of the upcoming approaches that enables enhanced biocompatibility while providing a delivery vehicle for proteins. Similarly, physical adsorption, radiation mediated modifications, grafting, and protein modifications are other methods that have been employed successfully for alterations of surface properties of polymeric scaffolds. The goal of this review is to provide an overview of the role of surface properties /chemistry in tissue engineering and briefly discuss some of the methods of surface modification that can provide improved cell and protein interactions. It is hoped that these improved polymeric scaffolds will lead to accelerated and functional tissue regeneration.