This chapter provides an overview of how bone cells coordinate their actions to generate, maintain, and remove bone mass. As a dynamic connective tissue, bone is constantly responding to external forces, such as loading of the skeleton and to internal and external signals, such as cytokines, growth factors, and hormones. In addition to external signals, bone cells are in constant communication with each other and cells of the immune and hematopoietic systems, through factors, such as osteoprotogerin, RANKL, ephrins, and sclerostin. The extracellular matrix (ECM) on which osteoblasts and osteoclasts attach and in which osteocytes reside, influences the function of these cells. The cells that resorb the mineralized ECM of bone are called osteoclasts. They arise from hematopoietic progenitors that also give rise to macrophages. The osteoclasts precursor cells are recruited to the bone surface where they fuse to form multinucleated cells. The second factor is osteoblasts; it is the cells that form bone, characterized by their unique ability to secrete a type I collagen-rich ECM that eventually mineralizes. Osteoblasts arise from multipotent progenitor cells of mesenchyme origin, mesenchymal stem cells. The third factor is osteocytes that possess a very unique location in bone, being trapped within lacunae similar to small "caves" inside the bone matrix, where the cells form a connective network by sending their dendritic processes through small "tunnels," called canaliculi, that connect and span throughout the whole bone volume. The proposed main function of osteocytes is to sense distribution and amount of mechanical strain that is applied to the bone.