Osteoclasts are multinucleated cells formed by the fusion of mononuclear precursor cells. It is generally agreed that their immediate precursors, referred to here as preosteoclasts, are derived from the monocyte-macrophage lineage, and so ultimately from the hematopoietic stem cell, and that their fusion product resorbs bone2, 36, 40, 41; however, what happens in between these processes is much less clear. Preosteoclast production occurs in hematopoietic (red) marrow, which in the adult is restricted to the central skeleton. 42 Bone resorption occurs at endosteal and, to a much lesser extent, periosteal bone surfaces throughout the skeleton. Preosteoclasts are known to circulate9 and in the peripheral skeleton the circulation provides their only access route to bone surfaces, 13, 43 via the sinusoid occupying the center of each basic multicellular unit (BMU), which is the instrument of bone remodeling (Figure 1). 26 In the central skeleton, direct migration of preosteoclasts from red marrow to bone surfaces seems possible, and is frequently assumed to occur, but has not been demonstrated directly. The close spatial association between endothelial cells1 and vascular sinusoids22, 23 and sites of surface remodeling suggests that, even in central cancellous bone, adjacent to red marrow, the structure of the BMU is essentially the same as in cortical bone, and that many osteoclasts are derived from circulating rather than from locally migrating precursors. 26