It has been demonstrated that human osteoblastic as well as osteoclastic cells are equipped with adrenergic receptors and neuropeptide receptors and that they constitutively express diffusible axon guidance molecules that are known to function as a chemoattractant and/or chemorepellent for growing nerve fibers. These findings suggest that the extension of axons of sympathetic and peripheral sensory neurons to osteoblastic and osteoclastic cells is required for the dynamic neural regulation of local bone metabolism. Recently, bone resorption modulated by sympathetic stimulation was demonstrated to be associated with ODF (osteoclast differentiation factor) and OCIF (osteoclastogenesis inhibitory factor) produced by osteoblasts/stromal cells. This review summarizes the evidence implicating sympathetic neuron action in bone metabolism. The possible function of osteoclastogenesis, which could result in the initiation of sympathomimetic bone resorption, is also discussed. Microsc. Res. Tech. 58:77–84, 2002. © 2002 Wiley-Liss, Inc.