An implant enters a host during trauma, the wounding process of surgery. Trauma initiates a healing course that naturally progresses through inflammatory and repair phases before host tissue settles down to scar or in some tissues progresses to regeneration. The presence of an implant alters healing if only by occupying space once filled with host tissue. In the most desirable scenario host tissue returns to normal function at a level above the condition that initiated implantation, and soon enough to ensure the overall health of the patient. The ability of an implant to achieve this goal is a measure of its biocompatibility as defined by Jonathan Black. There is ample evidence to warn any implant developer that host tissue is aware of the foreign object it surrounds, from nanoparticles to lung transplants. Response to the construct may range from coating it with a thin layer of fibroblasts to development of life-threatening anaphylactic shock. A successful biomaterials developer understands host wound healing physiology in the presence of an implant well enough to anticipate and reduce undesirable host responses. Where surgical trauma was preceded by an injury that opened skin, there is the complication of infection to anticipate. Host reaction begins with a molecular race to initiate a biofilm on the implant surface. The critical molecules are proteins like albumin and complement. Within seconds platelets and then cells adhere to the molecular film. These cells are also in the race for the surface. Those that remain adhered to the film are often determined by the molecular composition of the film. If some of these cells are bacteria the future of the implant is in danger. The most influential adherent cell at this stage is the macrophage. Macrophages direct the healing process and decide if implant material is a threat. If the biomaterial is deemed a threat a foreign body reaction will be initiated. This response is part of what is called the innate immune response that is initiated by attached complement. The function of an FBR is to destroy the threat. Failing this, macrophages will direct walling it off from healthy host tissue with scar tissue. Innate immunity gets its name from the fact that it is programmed and prepared to operate before triggered by any implant. Natural selection in the form of rapid bacterial evolution has pushed higher animals to develop responses to materials not covered by innate immunity. These come from the adaptive immune system and involve lymphocytes. The interaction of macrophages, lymphocytes and a close relative of macrophages, dendritic cells creates a rather complex scheme of host reaction to implants that challenge the design of biomaterials meant reside for long terms in human hosts. Recent discovery of previously unknown ways by which these cells communicate with each other (e.g. Toll-like receptors) intensify the challenge. As the implant ages and appears to have achieved compatibility, a new challenge may emerge. Wear. Corrosive body fluids and abrasion may create effectively new materials. Wear particles and metal ions not released by the original implant may challenge the host. Bacteria that succeeded in forming a biofilm at implantation may grow colonies large enough to break the film membrane and spread infection into surrounding tissue. Consideration of these possibilities may induce an implant designer to consider inclusion of removal facilitation in the original design. Recently a number of laboratories have designed anti-bacterial films to block establishment of biofilms. These challenges will be described in more detail.