Autografts have consistently outperformed calcium phosphate implants in most experimental models and clinical applications. However, human trials in metaphyseal defects demonstrate comparable results with autograft, hydroxyapatite, and TCP. Diaphyseal fractures and segmental defects represent more challenging problems, with less predictable results achieved with the synthetic bone graft substitutes. Improvements in the pore configuration, mechanical properties, and osteoinductive capacity of these implants should widen their future clinical application.