The osteoclast is the major agent of bone resorption. Durang the last few years persuasive evidence has emerged from several sources which shows that the osteoclast is derived from the fusion of cells of the mononuclear phagocyte system. This fact makes a reevaluation of the pathophysiology of bone resorption necessary. The most plausible mechanism for osteoclast formation is that bone-lining alter bone locally in such a way as to lead to its phagocytic recognition by mononuclear phagocytes. These cells then accumulate on the altered bone surface, commence digestion, and fuse in a similar way to that shown for other macrophage polykaryons. Once formed, osteoclast function may be influenced in two ways: some agents, such as osteoclast-activating factor and lipopolysaccharide, may directly stimulate osteoclast resorptive activity, in the same way as they influence the activity of other cells of the mononuclear phagocyte system; other agents, such as parathormone and prostaglandins, because they also cause in increase in the number of osteoclasts, seem more likely to have a primary effect on bone-lining cells, which in turn regulate osteoclast activity by unknown mechanisms.