Bone marrow stromal cells can undergo adipogenesis or osteoblastogenesis in vitro and in vivo. This review explores the stromal cell's differentiation plasticity in the context of osteoporosis and other metabolic bone disorders. Attention is focused on the apparent reciprocal relationship that is postulated to exist between the adipocyte and osteoblast phenotypes. The signal transduction pathways implicated in this process are evaluated as potential targets for therapeutic intervention and drug design.