Mesh biocompatibility is basically determined by the foreign body reaction (FBR). In contrast to physiological wound healing and scar formation, the FBR at the host-tissue/biomaterial interface is present for the lifetime of the medical device. The cellular interactions at the mesh/tissue interface proceed over time ending up in a chronic inflammatory process. The time course of the FBR has been studied extensively and consists of three crucial steps that are protein absorption, cell recruitment and, finally, fibrotic encapsulation and extracellular matrix formation. Each of these steps involves a complex cascade of immune modulators including soluble mediators and various cell types. Recent research has focused on the cellular and molecular interactions of the distinct phases of the FBR offering a new basis for therapeutical strategies. The highly dynamic process of the FBR is considerably influenced by the biomaterial composition. Modifications of the type of polymer, the material weight, the filament structure and the pore size are realized and have substantial effects on the in vivo biocompatibility. Moreover, modern mesh technology aims to utilize the available implants as carrier systems for bioactive drugs. Studies in animal models account for the efficiency of these drugs that aim to reduce mesh-related infections or to minimize FBR by influencing inflammation or extracellular matrix remodelling. A thorough understanding of the molecular mechanisms of FBR provides a sophisticated background for the development of new biomaterials at least as carrier systems for bioactive reagents to reduce inflammation and to improve clinical outcome.