Although biologic indices of bone turnover are widely accepted as research tools in population-based studies, their clinical utility in the management of the individual patient remains controversial. Their main limitation for a routine clinical use is related to an important biologic variability, which means that large variations (ie, in response to therapy) are needed to consider a difference between two measurements as reflecting a significant biologic change. To date, the most valuable bone markers are serum osteocalcin, bone-specific alkaline phosphatase, and the N-terminal propeptide of type 1 procollagen for bone formation and urinary measurements of the phenazopyridine crosslinks and related telopeptides for bone resorption. New serum assays for both C-telopeptide and N-telopeptide of type 1 collagen seem promising but need extensive validation. Although bone markers provide little information in the diagnosis of osteoporosis, strong evidence now shows that they can predict, albeit imperfectly, the rate of bone loss in menopausal women and the response to some antiresorptive therapies. In some populations, increased bone turnover has been shown to be a strong predictor of fracture risk, independently and to the same extent as low bone density. Whether bone markers are used to monitor the efficacy of (or compliance with) a specific treatment or to identify patients at risk for osteoporosis and thus to target preventive therapy, cost-benefit analysis, and evaluation of the potential improvement in patient outcome are clearly needed before these parameters may be universally accepted as tools to optimize patient care.