The aim of this review was to elucidate the origins of research about xenogeneic grafts and to correlate it history with pre-clinical and clinical results, screen up the origins and the innovations through its laboratorial and clinical applications.Background: The use of xenogeneic materials has been reported in medicine for the past two centuries.Bone regeneration procedures are an important part of oral and maxillofacial surgery development, either to repair aesthetic defects or to reestablish function. With the rising of dental implants research and techniques, bone augmentation became an essential also for oral implantology.Methods: A comprehensive search, without date limit was performed in MEDLINE, SCOPUS, Cochrane and Web of Science databases, systematic reviews, human studies, clinical reports, in vivo and in vitro studies regarding history, application, outcomes or innovations in xenogeneic bone grafts usage were included, after initial search a manual cross-reference search was performed in the included papers.Conclusions: Despite autologous bone being the reference biomaterial, its limited amount, need of donor site and associated morbidity enhance the search for suitable bone substitutes. Therefore, xenogeneic grafts have been pointed as one of the most reliable alternatives to autogenous bone in augmentation techniques, but even with plenty of clinical data and empirical expertise, there is no consensus about its properties, fabrication methods and biological mechanisms which leads to clinical success.