Osteoclasts, the main protagonists involved in bone resorption mechanisms, are generally considered to be of haematopoietic origin, although the exact nature of the primary osteoclastic stem cells is still unknown. In vitro cellular models developed to study the different events of osteoclastic differentiation have revealed that not only several cell types (osteoblasts, monocytes, lymphocytes, etc.) but also many soluble factors (cytokines, hormones, vitamins, ions, etc.) and extracellular matrix elements (osteopontin, osteocalcin, etc.) are involved in osteoclastic differentiation and activation. This article provides an exhaustive review of recent knowledge on the origin of the osteoclast and the main substances involved in the osteoclastogenesis and activation of these cells.