The first generation of synthetic bone substitute materials (BSM) was initially investigated in the mid 1970s using hydroxyapatite (HA) as a biomaterial for remodeling of bone defects. The concepts established by CPC pioneers in the early 1980s were used as a platform to initiate a second generation of BSM for commercialization. Since then, advances have been made in composition, performance and manufacturing. A self-setting and injectable calcium phosphate cement (CPC) based on amorphous calcium phosphate (ACP) with calcium to phosphate (Ca/P) atomic ratio less than 1.5, combined with dicalcium phosphate dihydrate (DCPD or brushite, seeded with apatite), is proposed. Amorphization of raw material was observed following high energy mechano-chemical processing. Upon hydration, the cement hardened in less than 3 minutes at 37°C and reached a maximum compressive strength of about 50 MPa. The final product was a low crystalline calcium deficient carbonated apatite similar to the composition and structure of bone mineral. In vivo performance of this cement in mediating bone healing was compared to α-BSM® in a rabbit femoral defect model. Performance characteristics of some commercially available CPC products are compared. The concerns of CPC designers and the needs of product users (surgeons) are discussed.