Bone remodelling is an active and dynamic process that relies on the correct balance between bone resorption by osteoclasts and bone deposition by osteoblasts. Moreover, these two functions must be tightly coupled not only quantitatively, but also in time and space. When the coupling is lost, the correct bone mass could be compromised, leading to several skeletal pathologies. Indeed, bone loss and osteoporosis are the result of an increased osteoclast function and/or a reduced osteoblast activity. In contrast, other pathologies are related to osteoclast failure to resorbe bone, such as osteopetrosis, a rare genetic disorder characterized by an increased bone mass and also linked to an impairment of bone marrow functions. Starting from these assumptions, it is necessary to more deeply understand the molecular mechanisms regulating bone cell functions. Indeed, recent studies evidenced a complex interplay between the immune and skeletal systems, which share several regulatory molecules including cytokines, receptors and transcription factors. These data allowed to more deeply understand the mechanisms underlying bone mass regulation and could open new avenue to identify target molecules for alterantive therapies more efficacious against bone diseases.