The repair of complex abdominal wall defects remains one of the most challenging procedures facing reconstructive surgeons. Through these collaborative efforts, defects that were once thought to be impossible to reconstruct can now be repaired, and patients who were left to a miserable quality of life are now offered hope. Among the most important advances in this field have been the adoption of component separation and many of its modifications, the development of new lightweight synthetic mesh, and the explosion of biologic mesh into the surgical armamentarium of the reconstructive surgeon. While biologic grafts are gaining in popularity, the molecular processes and host reactions to biologic grafts are not only unclear but often misunderstood and misrepresented. As a result, comprehensive analysis of basic science concepts presented in this review should help a practicing surgeon with understanding what biologics actually do and what we can expect biologic meshes to accomplish. This article focuses on summarizing the current basic science evidence and the clinical outcomes of utilization of these grafts published in the peer-reviewed literature.