Bone regeneration is a well organized but complex physiological process, in which different cell types and their activated signaling pathways are involved. In bone regeneration and remodeling processes, mesenchymal stem cells (MSCs) have a crucial role, and their differentiation during these processes is regulated by specific signaling molecules (growth factors/cytokines and hormones) and their activated intracellular networks. Especially the utilization of the molecular machinery seems crucial to consider prior to developing bone implants, bone-substitute materials, and cell-based constructs for bone regeneration. The aim of this review is to provide an overview of the signaling mechanisms involved in bone regeneration and remodeling and the osteogenic potential of MSCs to become a key cellular resource for such regeneration and remodeling processes. Additionally, an overview of possibilities to beneficially exploit cell signaling processes to optimize bone regeneration is provided.