Osteoclasts are large, multinucleated cells which change their shape and polarity according to their resorptive activity. At least in vitro, nonresorbing osteoclasts move on the bone surface and do not show clear evidence of apical-basolateral polarity. When stimulated for resorption, osteoclasts undergo a rapid reorganization of the cytoskeleton and appear clearly polarized. The detailed nature of different membrane domains in polarized osteoclasts is still far from clear, but a remarkable feature is the formation of a tight sealing zone between the ruffled border and the rest of the cell membrane. Characteristic organization of F-actin into a belt or ring-like structure with a double circle of vinculin around it is needed for the formation of the sealing zone. This type of microfilament organization is typical only for resorbing osteoclasts and can thus be used as a marker for resorbing cells. These characteristic changes in the molecular organization of the cytoskeleton in osteoclasts during the resorption cycle offer several potential targets to inhibit bone resorption, perhaps cell-specific.