Osteocalcin is an abundant Ca2+-binding protein indigenous to the organic matrix of bone, dentin, and possibly other mineralized tissues. This protein contains 47–50 amino acid residues (molecular weight 5,200–5,900) depending on the species. Osteocalcin is distinguished by its content of three gamma-carboxyglutamic (Gla) residues. The vitamin-K-dependent biosynthesis of osteocalcin occurs in bone, and the protein is not homologous to the Gla-containing regions of known vitamin-K-dependent blood coagulation proteins. The two major structural features of osteocalcin which appear to control its function include: (1) the ‘Gla helix’, a compact Ca2+-dependent alpha-helical conformation, in which the three Gla residues are aligned to facilitate adsorption to hydroxyapatite, and (2) the ‘COOH-terminal beta-sheet’ which exhibits chemoattractant activity toward mononuclear leukocytes, specifically monocytes, the putative precursors of osteoclasts. While the biological function of osteocalcin is unknown, it appears to be a highly specific osteoblastic marker produced during bone formation, and is rapidly becoming a clinically important diagnostic parameter of bone pathology. This article reviews recent advances in the understanding of osteocalcin.