Bone formation takes place throughout life in order to support growth, mechanical forces, bone turnover to meet metabolic needs, and the reparative process. The requirement for continuous renewal of bone through the remodeling process necessitates recruitment, proliferation, and differentiation of osteoblast-lineage cells. A contributing factor to bone loss in the aging skeleton is the decreased ability of bone-forming osteoblasts to replace bone removed by the activity of the bone-resorbing osteoclasts. It is now appreciated how numerous developmental, growth factor, cytokine, and hormone-responsive regulatory signals mediate competency for expression of genes associated with bone matrix synthesis and metabolic responses as a function of the stages of osteoblast growth and differentiation.