The use of soluble signals for modulation of bone formation has become a significant area of clinical research in recent years. Improvements in implant site preparation and osseointegration have already been achieved with the use of recombinant platelet-derived growth factor and bone morphogenetic proteins on osteogenic scaffolds. Other states of insufficient bone such as osteoporosis are frequently treated with inhibitors of osteoclast function or osteoblast anabolic agents. However, despite the existence of promising therapies targeting osteoblasts and osteoclasts directly, therapies utilizing indirect regulation through secondary cellular nodes of control (NOC) are just beginning to emerge. This article will review current strategies for regulation of bone formation by targeting two primary NOCs, the osteoblast and osteoclast, as well as four secondary NOCs, the vascular, hematopoietic, mesenchymal, and neural. Keywords: bone, cell signaling, dental implant, differentiation, growth factors, regeneration, tissue engineering