In the somatosensory system, P2X receptors are expressed on both peripheral and central terminals of primary afferent neurons. Those expressed on peripheral terminals are activated in response to both nociceptive and innocuous stimuli, whereas those at central terminals ("central terminal P2X receptors") play an important role in modulating sensory transmission to the spinal cord dorsal horn. The author reviews recent studies on the central terminal P2X receptors. It is proposed that central terminal P2X receptors, once activated, may be involved in both central sensitization and initiation of pain. Thus, these receptors may represent a promising target for therapeutic management of pathological pain.