- The foreign body response (FBR) occurs ubiquitously to essentially all non-biological materials that are implanted into higher organisms. The FBR is characterized by inflammation followed by fibrosis and is mediated largely by macrophages. While many current medical devices tolerate the FBR, the FBR is responsible for many asceptic device failures and is hindering advancements of new devices that rely on device-host communication to function. To this end, in vitro and in vivo models are critical to studying how a biomaterial, via its chemistry and properties, affect the FBR. This short review highlights the main in vitro and in vivo models that are used to study the FBR. In vitro models that capture macrophage interrogation of a biomaterial and evaluation of macrophage attachment, polarization and fusion are described. In vivo models using rodents, which provide a relatively simple model of the complex FBR process, and human-relevant nonhuman primate models are described. Collectively, the combination of in vitro and in vivo models will help advance our fundmental understanding of the FBR and enable new biomaterials to be developed that can effectively modulate the FBR to achieve a desire device-host outcome.