THE IDENTIFICATION OF mutations in the human low-density lipoprotein (LDL) receptor–related protein 5 (LRP5) gene that give rise to conditions of low bone mass (1, 2) and increased bone mass (3–5) has brought what just a few years ago were two seemingly unrelated fields crashing together, namely bone biology and Wnt signaling. It is now clear that the Wnt signaling pathway is another key pathway involved in the regulation of bone mass. This is not to diminish the importance of any other pathway that is known to play a role; rather, this discovery only highlights how little we probably really know about bone mass regulation. Certainly, a big challenge we now face will be to integrate the Wnt signaling pathway with all of its complexities and subtleties into the already complex nature of the other pathways that have been studied, with the ultimate goal of developing a composite understanding of their collective roles and interactions. In this article, we will summarize the main points of our current understanding of LRP5, Wnt’s and Wnt signaling, and the role they may play in bone. This is by no means comprehensive, and there are more unanswered questions than answers.