Systemic hormones and cytokines play important roles in regulating both osteoblast and osteoclast activity. These cytokines can have either positive or negative effects on the growth and differentiation of bone cells. These effects appear to be dependent on the model systems use to assess them, as well as the species tested. In the near future, other autocrine-paracrine factors will be identified that enhance osteoblast and osteoclast activity, and model systems should be available to further delineate their effects on cells in the osteoblast lineage. Use of transgenic mice with genes targeted to the osteoblast and osteoclast may further reveal the mechanisms responsible for the growth and differentiation of these cells, as well as produce immortalized cell lines that more accurately reflect the cell biology of the osteoclast and osteoblast in vivo.