The last 5 yr have witnessed major progress in skeleton biology. One of these areas of progress has been the partial elucidation of the transcriptional mechanisms of osteoblast differentiation and their conservation between mouse and human. Cbfal, or runx2, a homolog of the Drosophila Runt protein serves both as the earliest transcriptional regulator of osteoblast differentiation and as controller of bone formation by already differentiated osteoblast. Moreover, Cbfal is also a hypertrophic chondrocyte differentiation factor in several skeletal elements. Although other transcription factors are likely to be involved in osteoblast differentiation, Cbfal, by the multiplicity of the role that it plays, can be viewed as the central regulator of intramembranous and endochondral ossification.