 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 reaction, impacting biocompatibility and success in tissue engineering and regenerative medicine. The focus of this review is on the interactions between 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, monocyte slash macrophage adhesion, fusion to form foreign body giant cells, and modification of the biomaterial surface. Physical chemical 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 following biomaterial implantation, we can design novel biomaterials-based tissue-engineered constructs that elicit a favorable immune response and perform for their intended applications. This article was authored by Zhishan Shik, Patricia J. Brooks, Oriya Barzale, and others. We are article.tv, links in the description below.