The deleterious effect that biofouling has on sensor stability is a serious impediment to the development of long term implanted biosensors. This paper reviews the surface modification strategies currently employed to minimize membrane biofouling of in vivo sensors. Nine sensor modifications are discussed herein: hydrogels, phospholipid-based biomimicry, flow-based systems, Nafion, surfactants, naturally derived materials, covalent attachments, diamond-like carbons, and topology.