Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-beta family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-beta, and third IGF-I. TGF-beta enhances bone formation mainly by intramembranous ossification in vivo. TGF-beta affects both cell proliferation and differentiation, however, TGF-beta mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-beta is increased by estrogen(E2), androgen, vitamin D, TGF-beta and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.