Prostaglandins (PGs) are potent stimulators of bone formation and resorption and are produced by bone cells. PGs also have inhibitory effects on fully differentiated osteoblasts and osteoclasts. This complex, multifunctional regulation is probably mediated by different PG receptors. Endogenous PGs in bone are produced largely by induction of COX-2, which is highly regulated by hormones and local factors. The development of specific agonists and antagonists for PG receptors and for COX-2 should allow us to define the physiologic and pathophysiologic roles of PGs more precisely and develop new therapeutic approaches to metabolic and inflammatory disorders of the skeleton.