The balance between all the signalling molecules involved in bone formation with their inhibitors and most importantly between BMPs and their antagonists is critical determinant of osteogenesis, and therefore of skeletal development, fracture repair, and bone remodelling. The main identified inhibitory molecules of the osteogenic lineage, either from studies during embryonic development or from in vitro and in vivo studies are presented in the herein study. Potential treatments using these molecules either alone or in combination with BMPs to control the bone growth and overgrowth are already under investigation aiming in treatments that mimic as much as possible the natural process of bone generation in various situations including fracture healing, osteoporosis, and osteoarthritis and other metabolic disorders, in order to more closely resemble the original tissue.