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