The vitamin K-dependent protein of bone, osteocalcin (bone Gla protein) is a specific product of the osteoblast. A small fraction of that synthesized does not accumulate in bone but is secreted directly into the circulation. Upon catabolism of osteocalcin, its characteristic amino acid, gamma-carboxyglutamic acid (Gla), is excreted into the urine. Both serum osteocalcin and urine Gla are currently being used for the clinical assessment of bone disease. The authors summarize the current understanding of the structure and function of osteocalcin in bone and evaluate the clinical studies done using serum osteocalcin and urinary Gla to monitor bone turnover. Factors that affect the measurement of osteocalcin concentrations in the blood are osteoblastic synthesis, content of Gla in the protein, drug-induced alterations in osteocalcin's affinity for bone, hormonal status, renal function, age, sex, timing of blood collection, and specificity of the radioimmunoassay. With these considerations, serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism.