Glutamatergic signaling is implicated in the pathophysiology of several psychiatric disorders, including schizophrenia and major depression. While the ionotropic glutamate receptors in particular are believed to play an important role in these disorders, more recent interest has focused on the metabotropic class of glutamate receptors. Metabotropic glutamate receptors (mGluRs) have been identified as exciting novel therapeutic targets for the treatment of schizophrenia and major depression, showing promising evidence in preclinical models. However it is important to consider the status of mGluRs in the pathophysiology of these disorders as this may influence the therapeutic ability of this novel class of mGluR-targeting drugs. Furthermore, it is necessary to determine whether current therapeutics indirectly influence mGluRs as this may provide some understanding of the effects of the use of these novel drugs as adjuncts with current therapeutics. In this chapter we review the literature on the role of mGluRs in schizophrenia and major depression. We also review the studies assessing whether current antipsychotic and antidepressant therapeutics mediate their effects through mGluRs and we examine the potential of novel therapeutics targeting these receptors.