Bone tissue engineering is expected to be utilized clinically as a patient friendly strategy instead of autogenous bone grafts, and bone morphogenetic protein (BMP) is applying for bone regeneration. BMPs have been found in the 1960s and their gene cloning has been succeeded two decades later, which revealed that BMPs were members of TGF-β superfamily. BMPs have critical functions in embryonic development and tissue generation, and BMPs induce bone formation in mammals though its primary functions are different. Subcutaneous implantation of BMP in rodent reproduces endochondral bone formation occurred in embryogenesis. Recombinant human BMPs are applied for spinal fusion and non-union fracture repair and also utilized in the field of oral and maxillofacial surgery such as sinus floor augmentation. BMP regenerates mandible bone after its segmental resection in non-human primates as a preclinical trial. However, the results were not conclusive in clinical studies especially in elderly patients. A high dose of BMP is required to restore large bone defects, but it may also induce life threatening significant edema. The further studies are necessary for effective and safe application of BMPs to restore large bone defects.