Since the discovery of its role in the CNS, glutamate, together with its involvement in signalling at synapses, has been the subject of a vast amount of research. More recently, it has become clear that glutamate signalling is also functional in non-neuronal tissues and occurs in sites as diverse as bone, pancreas and skin. These findings raise the possibility that glutamate acts as a more widespread 'cytokine' and is able to influence cellular activity in a range of tissue types. The impact of these discoveries is significant because they offer a rapid way to advance the development of therapeutics. Agents developed for use in neuroscience applications might be beneficial in the modulation of pathology peripherally, impacting on conditions such as osteoporosis, diabetes and wound healing.