In recent years, major advances have been accomplished in abdominal wall reconstruction. Introduction of newer prostheses have improved outcomes, but elimination of mesh‐related morbidity is still an elusive issue. It is believed that host foreign body reaction to prosthesis plays an important role in the biology of these complications, so understanding of the molecular mechanisms behind mesh–tissue interactions may be a key for upcoming therapies. It appears that increasing biocompatibility of both synthetic prosthesis and biologic scaffolds might be the main avenues to achieve better outcomes. This manuscript provides an overview of major effectors of wound healing with particular emphasis on how their modulation might improve outcomes in tissue remodeling and mesh integration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 295–302, 2014.