Bone replacement grafts are widely used to promote bone formation and periodontal regeneration. Conventional surgical approaches, such as open flap debridement, provide critical access to evaluate and detoxify root surfaces as well as establish improved periodontal form and architecture; however, these surgical techniques offer only limited potential in restoring or reconstituting component periodontal tissues. A wide range of bone grafting materials, including bone grafts and bone graft substitutes, have been applied and evaluated clinically, including autografts, allografts, xenografts, and alloplasts (synthetic/semisynthetic materials). This review provides an overview of the biologic function and clinical application of bone replacement grafts for periodontal regeneration. Emphasis is placed on the clinical and biologic goals of periodontal regeneration as well as evidence-based treatment outcomes.