Glutamate receptors (GluRs) are localized in the periphery on nociceptive primary afferent terminals. Studies in animal models of pain demonstrate that peripheral glutamate is involved in nociceptive transmission in the normal and the inflamed state and that modulation of peripheral GluRs reduces pain behaviors and nociceptor activity. These data provide strong motivation to develop new pharmacological agents that will target peripheral GluRs, offering novel approaches to treatment of pain of peripheral origin.