Mononuclear myeloid lineage cells, which are attracted to bone surfaces by chemokines and other factors, differentiate into multinucleated bone resorbing osteoclasts by cell fusion. Receptor activator of nuclear factor-κB ligand (RANKL) , which is expressed in mesenchymal cells, including osteocytes and hypertrophic chondrocytes, is essential for osteoclast differentiation and function. Osteoclasts have the capacity to resorb bone and impaired osteoclast differentiation and/or function leads to osteopetrosis, a rare disease in which mineralized bone cannot be removed. In contrast, excessive osteoclastogenesis causes diseases such as osteoporosis. Recent findings suggest that osteoclasts can also function as positive and negative regulators of osteoblastic bone formation. Thus, understanding of the molecular mechanisms that regulate osteoclastogenesis is important to develop therapeutic approaches to prevent bone diseases. This paper reviews recent findings of the molecular mechanisms regulating osteoclast differentiation and function.