Bone is a living tissue and is maintained by the coordinate action of osteoblasts and osteoclasts. The intercellular communication between these two cells is the quintessential mechanism in bone remodelling. The importance of this interaction is increasingly evident as disruption of this "cross-talk" results in debilitating bone diseases. It has been well established that osteoblasts can regulate osteoclast formation and activation via the production of osteoclastogenic factors. There are now several emerging investigations that have identified novel osteoclastderived factors that have the potential to control osteoblastic growth and function. This chapter highlights the intercellular communication between osteoblasts and osteoclasts and the impact of this "cross-talk" in bone diseases, including giant cell tumour of bone and other osteolytic bone tumours, osteoporosis, osteopetrosis, osteogenesis imperfecta, Paget’s disease, periodontitis, osteoarthritis and aseptic loosening.