There is now growing evidence that a number of multifunctional signaling molecules, originally discovered as signal molecules in specific cells, exert their effects in various other tissue compartments. Neurotrophins, a class of homologues growth factors initially discovered to promote neuronal growth and survival, display such a dual activity and contribute to the development of a variety of non-neuronal tissues. Nowadays, several examples of essential non-neuronal functions played by neurotrophins and of variations of neurotrophin expression that accompany these processes can be presented. As will be shown, neurotrophins are found in many body tissues produced by a variety of non-neuronal cell types such as immune cells, adipocytes, endothelia, epithelia, fibroblasts, keratinocytes and endocrine cells. Assuming a general role as growth and survival factors, changes in neurotrophin expression may reflect physiological or pathological processes, such as activation, proliferation or repair followed by injury in the tissues. Neurotrophins were also present in the systemic blood circulation and variations in blood concentrations indicate vascular as well as peripheral production. In this review, we will discuss changes in local and systemic neurotrophin concentrations as well as their known pathophysiological relationship in various inflammatory and non-inflammatory disorders. Beside the nervous system, these will include diseases of the airways, skin and joints as well as systemic autoimmune diseases. Furthermore, new aspects of neurotrophin actions in maintenance of body energy balance and in reproductive endocrinology will be presented.