An increasing number of studies suggest that nerve-derived signals play an important role in the regulation of bone remodeling. Neuropeptides and receptors/transporters of adrenergic, glutaminergic, serotoninergic, dopaminergic and sensory nature have been described in osteoblasts in vitro. Downstream signaling pathways and targets genes have been identified, but the in vivo relevance of these findings remained controversial until more recent gene gain and loss of function studies confirmed the role of CGRP and beta2-adrenergic receptor signaling in osteoblasts. Tissue and time-conditional mutant mice originally generated for studies unrelated to bone are now available tools to determine the role of neuronal signaling in bone and to dissociate the central and peripheral role of these signals. Lastly, understanding how the central nervous system integrates homeostatic signals with the regulation of bone homeostasis will be the next exciting subject of research in the field.