Bone remodeling is the process by which old bone is replaced by new, and it is carried out by teams of osteoclasts and osteoblasts that comprise the basic multicellular unit (BMU). The cellular hallmark of the osteopenia caused by estrogen deficiency is increased bone remodeling, which reflects initiation of new BMUs and/or an extension of the lifetime of existing ones, resulting in an imbalance of bone resorption over bone formation. 3, 21 An increase in the number of osteoclasts is an essential prerequisite for either the initiation of new BMUs or prolongation of existing BMU progression. 59 Therefore, elucidation of the pathogenesis of postmenopausal osteoporosis requires studies to determine the effects of estrogen on the cellular and molecular mechanisms that regulate osteoclast number. The purposes of this review are to summarize recent findings of such studies, and to develop a working model of how loss of estrogen leads to an increase in osteoclast number, and thereby increased bone remodeling and the development of osteopenia.