Host responses toward foreign implants that lead to chronic inflammation and fibrosis may result in failure of the biomedical device. To solve these problems, first a better understanding of the biomaterial?induced host reactions including protein adsorption, leukocyte activation, inflammatory and fibrotic responses to biomaterials is required; second an improved design of biomaterial surfaces is needed that results in an appropriate host response, causing less inflammatory response, and supporting tissue regeneration. Hence, this review provides a brief overview on the host response to implants, as well as in vitro models to study inflammatory and fibrotic responses to biomaterials to predict the clinical outcome of implantation. Moreover, the review highlights anti?inflammatory strategies to improve the biocompatibility of implants, which contain the modification of physicochemical surface properties of materials as well as the immobilization of anti?inflammatory reagents and bioactive molecules on biomaterials.