The clinically observed phenomena of allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (an increased response to a stimulus that is normally painful), which are the hallmarks of neuropathic pain, are expressions of "wind up" pain. Recent investigations indicate that this process can be prevented or mitigated by agents that block the effects of glutamate at the NMDA receptor. Other investigations have revealed that NMDA receptor antagonists can be useful in potentiating the analgesic efficacy of several classes of medication, including opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and local anesthetics. In addition, NMDA receptor antagonists may play an important role in mediating the development of opioid tolerance or in treating the perplexing syndrome of opiate-induced hyperalgesia.