Poly(tetrafluoroethylene) (PTFE), a fully fluorinated linear thermoplastic polymer, and in particular the porous form expanded PTFE (ePTFE) has found widespread use in biomaterials application due to its properties of high toughness, non-adhesiveness and hydrophobicity. While it performs ideally for many applications, some challenges have been identified for its use in small diameter vascular grafts and as a tissue space-filler for cosmetic reconstructions where the implant interfaces with bone. For these applications modification of the surface of ePTFE has been investigated as a means to enhance its performance. This review will focus on the applications listed above and will detail methods of evaluating the biological response, methods used to enhance the surface properties of ePTFE, and how the modified materials have performed in their intended applications. This review will focus on work published from 2004 onwards. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40533.