Bone is a complex organ system that provides structural support for the human body while also serving an important protective function for the internal organs. It is estimated that over 500,000 bone-grafting procedures are performed annually in the United States. These procedures have stimulated the pursuit of novel biomaterials with ideal properties. Key goals are to develop a biomaterial to replace bone that is inexpensive, biocompatible, radiolucent, resistant to infection, compressible, and replaced by host bone. The purpose of this review is to present the uses of commercially available bone grafts substitutes including allografts, calcium sulfates, calcium phosphates, and polymer materials. Descriptions of these biomaterials are provided in the context of their applications including craniofacial surgery, neurosurgery, fracture repair, dental and periodontal procedures, as well as pediatric reconstruction.