Osteoclasts are terminally differentiated multinucleated cells that are the principal resorptive cells of bone, playing a central role in the formation of the skeleton and regulation of its mass. The molecular events involved in the differentiation and function of osteoclasts had not been clarified for a long time. Over the past two decades, several novel approaches have been developed and adopted to investigate osteoclast biology. In the present review, we would like to update recent progress in the elucidation of the molecular mechanism of osteoclast activation and function.