The recent identification of a link between bone mass in humans and gain- or loss-of-function mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein 5 (osteoporosis pseudoglioma syndrome, high bone mass trait) or in the Wnt antagonist sclerostin (sclerosteosis, van Buchem syndrome) has called the attention of academic and industry scientists and clinicians to the importance of this signaling pathway in skeletal biology and disease. Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in regulating bone formation.