A recent unexpected development of bone biology is that bone is an endocrine organ contributing to the regulation of a number of physiological processes. One of the functions regulated by bone through osteocalcin, an osteoblast specific hormone, is glucose homeostasis. In this overview, we explain the rationale why we hypothesized that there should be a coordinated endocrine regulation between bone mass and energy metabolism. We then review the experiments that identified the endocrine function of osteocalcin and the cell biology events that allow osteocalcin to become a hormone. We also demonstrate the importance of this regulation to understand whole-body glucose homeostasis in the physiological state and in pathological conditions. Lastly we discuss the epidemiological and genetic evidence demonstrating that this function of osteocalcin is conserved in humans.