The last decade has seen an impressive expansion of our understanding of the role of osteocytes in skeletal homeostasis. These amazing cells, deeply embedded into the mineralized matrix, are the key regulators of bone homeostasis and skeletal mechano sensation and transduction. They are the cells that can sense the mechanical forces applied to the bone and then translate these forces into biological responses. They are also ideally positioned to detect and respond to hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts through the production and secretion of molecules such as Sclerostin and RANKL. How osteocytes perceive mechanical forces and translate them into biological responses in still an open question. Novel “in vitro” models as well the opportunity to study these cells under microgravity condition, will allow a closer look at the molecular and cellular mechanisms of mechano transduction. This article highlights novel investigations on osteocytes and discusses their significance in our understanding of skeletal mechano transduction.