The recent literature on the antinociceptive action of ionotropic glutamate receptor antagonists is reviewed with special emphasis on their clinical potential. Actually the glutamatergic pathways descending from the brain stem into the spinal cord may generate analgesia. However, physiologically more important is that glutamate and aspartate are apparently the main neurotransmitters along the ascending nociceptive pathways in the spinal cord. Glutamate, aspartate and their receptors can be detected in particularly high concentrations in the dorsal root ganglia and the superficial laminae (I, II) of the spinal cord. In low doses glutamate receptor antagonists only slightly elevate the threshold of the physiological pain sensation. However, they suppress the process of pathological sensitisation i.e. lowering of the pain threshold seen upon excessive or lasting stimulation of C-fibre afferents, a process that takes place during inflammation or other kinds of tissue injury. At electrophysiological level antagonists of both the NMDA- and AMPA / kainate receptors inhibit “wind up” i.e. lasting activation of the polymodal, second-order sensory neurones in the deeper layers of the dorsal horn. During sensitisation the resting Mg++ blockade of transmembrane Ca++ channels is abolished, certain second messenger pathways are activated, the transcription of many genes is enhanced leading to overproduction of glutamate and other excitatory neurotransmitters and expression of Na+ channels in the primary sensory neurones activated at lower level of depolarisation. This cascade of events leads to increased excitability of the pain pathways. NMDA antagonists are apparently more potent in experimental models of neuropathic pain, whereas AMPA antagonists are more effective in abolition of hyperalgesia seen during experimental inflammation. Clinically, of the previously known NMDA antagonists amantadine, dextromethorphan and ketamine have been tested, the latter extensively. Ketamine has been found quite active in certain cases of neuropathic pain and it reduced the opiate demand when used for postoperative analgesia. However, in other types of clinical pain their efficacy is less convincing. Not being registered there are no clinical data on the AMPA antagonists. There are, however, some investigational new drugs and some novel compounds in the stage of preclinical development which antagonise the AMPA receptors in competitive fashion or allosterically. Of the latter molecules 2,3-benzodiazepines are particularly promising.