Biomaterials are widely used to produce devices for regenerative medicine. After its implantation, an interaction between the host immune system and the implanted biomaterial occurs, leading to biomaterial-specific cellular and tissue responses. These responses may include inflammatory, wound healing responses, immunological and foreign-body reactions, and even fibrous encapsulation of the implanted biomaterial device. In fact, the cellular and molecular events that regulate the success of the implant and tissue regeneration are played at the interface between the foreign body and the host inflammation, determined by innate and adaptive immune responses. This chapter focuses on host responses that must be taken into consideration in determining the biocompatibility of biomaterial devices when implanted in vivo of animal models.