 Biomaterials induce cellular and tissue responses when implanted in vivo including inflammation, wound healing, foreign body reactions, and fibrous encapsulation. Macrophages are myeloid immune cells that ingest and degrade dead cells and foreign materials and orchestrate inflammatory processes. They are the dominant early responders to biomaterial implantation and remain at the interface for the lifetime of the device. Biomaterial surface properties play a crucial role in modulating the foreign body response, which may impact biocompatibility and success in tissue engineering and regenerative medicine. The focus of this review is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical, and morphological characteristics that regulate the foreign body response. Events include protein adsorption, monocytes slash macrophage adhesion, fusion to form foreign body giant cells, and modification of the biomaterial surface. Physicochemical cues on macrophages are not well understood, and there is a complex interplay between biomaterial properties and local environment. By understanding the role of macrophages in tissue healing processes, we can design novel biomaterials-based tissue engineered constructs that elicit a favorable immune response upon implantation and perform for their intended applications. This article was authored by Zishan Sheikh, Patricia J. Brooks, Orya Barzillay, and others. We are article.tv, links in the description below.