OSTEOCLASTIC BONE RESORPTION consists of several compli-cated processes: osteoclast development, attachment of osteoclasts to calcified tissues, development of a ruffled border and clear zone, followed by the secretion of acids and lysosomal enzymes into the space beneath the ruffled border. During the past decade, several new approaches have been taken to investigate osteoclast function. Highly purified functionally active osteoclasts can be isolated, which allows osteoclast function to be studied biochemically. The mechanisms of reduced bone resorption have been elucidated in several types of congenital osteopetrotic mutant mice. For example, the important role of macrophage-colony stimulating factor (M-CSF, colony-stimulating factor 1) in osteoclast development has been established in the osteopetrotic (op/op) mutant mice. Another osteopetrotic mutant mouse model has been generated by targeted disruption of the proto-oncogene c-src. Studies using this model showed that tyrosine kinase–mediated signals are essentially involved in osteoclast function. Using a purified osteoclast preparation, we showed that osteoclast function was activated by osteoblasts through a mechanism involving cell-to-cell contact. On the basis of these new approaches and experimental findings, we examined several fundamental issues regarding osteoclastic bone resorption. We considered how osteoclasts form ruffled borders and clear zones, which signals are necessary for osteoclast polarization, which mechanisms regulate the life span of osteoclasts, how calcitonin and bisphosphonates inactivate osteoclast function, and how osteoblasts regulate osteoclast function. In this article, we review the regulatory mechanisms of osteoclast function mainly on the basis of the experimental results obtained in our murine culture system.