The implantation of artificial organs, medical devices, or biomaterials results in injury and initiation of the inflammatory response. This inflammatory response to implants has as its components acute inflammation, chronic inflammation, foreign body reaction with granulation tissue, and macrophage and foreign body giant cell interactions. The form and topography of the surface of the artificial organ, medical device, prosthesis, or biomaterial can determine the composition of the foreign body reaction. The normal foreign body reaction consists of macrophages and foreign body giant cells at the surface of the implant with subjacent fibroblastic proliferation and collagen deposition, and capillary formation. Macrophages play a pivotal role in the response of tissue to implants. An hypothesis on the role of complement activation and complement-mediated cellular adhesion to implant surfaces has been presented. Macrophage adhesion and subsequent activation leading to cell-mediator and cell-cell communication is described.