There is a widespread presence of both adenosine (P1) and P2 nucleotide receptors in the brain on both neurones and glial cells. Adenosine receptors play a major role in presynaptic neuromodulation, while P2X receptors are involved in fast synaptic transmission and synaptic plasticity. P2Y receptors largely mediate presynaptic activities. Both P1 and P2 receptors participate in neurone-glia interactions. Purinergic signalling is involved in control of cerebral vascular tone and remodelling. Examples of the roles of purinoceptors in neuropathology involve: A(2A) receptors in Parkinson's disease and epilepsy, P2 receptors in trauma, ischaemia. Neuroinflammatory and neuropsychiatric disorders, and neuropathic pain.