This article focuses on one of the major failure routes of implanted medical devices, the foreign body reaction (FBR)that is, the phagocytic attack and encapsulation by the body of the so-called biocompatible biomaterials comprising the devices. We then review strategies currently under development that might lead to biomaterial constructs that will harmoniously heal and integrate into the body. We discuss in detail emerging strategies to inhibit the FBR by engineering biomaterials that elicit more biologically pertinent responses. Biotechnol. Bioeng. 2012; 109:18981911. (c) 2012 Wiley Periodicals, Inc.