Recent anatomical and behavioral data show the expression of G-protein coupled metabotropic glutamate receptors in the periphery on nociceptive primary afferent nerve terminals, and provide evidence for a functional role of peripheral metabotropic glutamate receptors in inflammatory pain. These findings have important implications for new therapeutic strategies that target peripheral metabotropic glutamate receptors for pain relief. They also alert us to the necessity of assessing drug effects at different levels of the nervous system: peripheral and central.