Bone morphogenetic proteins (BMPs) were purified from demineralized bone matrix by their ability to induce new bone formation in vivo. BMPs represent a large sub-family of proteins structurally related to TGF-beta and activins. Two BMP bone graft substitutes, BMP2 (InFuse®) and BMP7 (OP1®) have been developed as products for the repair of long bone non-union fractures and lumbar spinal fusion in humans. The approval of BMP2 and BMP7 based products for use in the clinic supports that the signals responsible for bone formation at ectopic sites can form a basis as therapeutics for bone repair and regeneration. This article describes a historical perspective of the discovery BMPs.