The management of long bone defects continues to be associated with significant challenges for optimum and timely bone repair. When bone grafting is needed, essential parameters to be addressed include adequate volume, optimum density, and structural capacity as well as potent biological properties. Although the autologous iliac crest bone graft remains the gold standard, its reduced availability and donor site morbidity have made the clinicians to seek for other alternative options. Reamer irrigator aspirator graft with materials used as graft expanders along with inductive molecules and cellular augmentation constitute the current trend for optimum bone regeneration. This article presents the contemporary thinking of the biological facet of segmental bone loss reconstruction.