For a long time the only functions attributed to the skeleton were locomotion and calcium storage. Over the last decade, this view has changed. Genetic studies in mice have shown that bone metabolism is regulated by the autonomic nervous system and interacts with energy metabolism and reproduction. Osteocalcin, one of the main organic ingredients of the bone matrix, was discovered to stimulate insulin production by the pancreas, as well as energy expenditure and insulin sensitivity. Administration of recombinant osteocalcin to mice on a high fat diet decreased weight gain and insulin resistance. These unanticipated results stimulated studies on osteocalcin and glucose metabolism in humans. This review will discuss these clinical studies and their perspective for the future.