There is a growing appreciation of the neural control of the skeletal system. Nerve fibers are found not only in the periosteum of bone, but also in cortical and trabecular portions of bone, and in the bone marrow. In addition to their important sensory roles and participating in vascular function, evidence increasingly shows that signaling molecules in skeletal nerve fibers may contribute to the regulation of bone cell function. In this review, the presence of receptors for skeletal neurotransmitters on osteoblasts and osteoclasts and the capacity of these receptors to regulate bone formation, osteoclast formation, and osteoclast activity are described. These observations, together with data obtained by chemically and surgically targeted nerve deletion, offer firm support for a view that suggests an important role of neural tissue in skeletal function.