From the onset of its discovery, the mGlu1 receptor has been postulated to play an important role in nociception processing based on the stoichiometry and location of receptor expression in the mammalian brain, in the spinal cord, and on peripheral nerve endings. Intrathecal injection of group I mGlu agonists were shown to increase the response to noxious stimuli in the dorsal horn. Antibodies and antisense reagents against mGlu1 were then discovered that reduced hyperalgesia and allodynia in rodent models of chronic pain, underscoring the hypothesis that antagonists of the mGlu1 receptor could be developed into useful tools for the treatment of pain. Early research from academia and the pharmaceutical industry led to rigid amino acid derivatives of glutamate as competitive antagonists. Unfortunately these were not developed into successful drug candidates because of their inadequate physiochemical characteristics along with their poor selectivity, potency, and brain penetration. The next advance came from the discovery of the noncompetitive antagonists. While noncompetitive mGlu1 antagonists have not been developed into drug candidates for the treatment of pain, they have further validated antagonists of the mGlu1 receptor as attractive drug targets. Fortunately, the large array of structural diversity found in the noncompetitive mGlu1 antagonists provides optimism that the proper balance of in vitro and in vivo antinociceptive activity can be identified, which bodes well for a drug candidate to emerge via this interesting and potentially beneficial target for persistent pain.