Osteoclasts, the principal bone-resorbing cells, not only play an essential role in skeletal development and maintenance but are also implicated in the pathogenesis of various bone disorders. Osteoclasts are giant cells that possess distinct morphological features, including mutlinucleation, polarization, ruffled border membrane, a unique cellbone matrix attachment and special cytoskeleton organization. Osteoclasts differentiate from mononuclear precursors of monocyte/macrophage lineage upon the stimulation of two key factors: M-CSF and RANKL. In addition, osteoclast differentiation is also modulated by a variety of other osteotropic factors such as la,25(OH)2 vitamin D3, dexamethasone, IL-1, TNF-a, prostaglandin E2, IL-11, PTH and estrogen. Osteoclastic bone resorption involves several major steps. It starts with the establishment of a functional resorption compartment and then the formation of ruffled border membrane facing bone. The ruffled border membrane is highly rich in proton pumps which transport protons into the resorption compartment to dissolve inorganic components of bone matrix. Onorganic component of bone is then degraded by various proteolytic enzymes also released through the ruffled border membrane. Finally, degraded products are removed outside of the resorption compartment by transcytosis.