The group I metabotropic glutamate receptors, mGluR1 and mGluR5, exhibit a high degree of sequence homology, and are often found co-expressed in the same neuronal populations. These receptors couple to a broad array of effector systems, and are implicated in diverse physiological and pathophysiological functions. Due to the high degree of sequence homology, and the findings that these receptors couple identically in recombinant systems, it has been generally assumed that these two group I mGluR subtypes would exhibit redundant function when co-expressed in the same neurons. With the advent of subtype-selective pharmacological tools, it has become possible to tease apart the functions of mGluR1 and mGluR5 in the same neuron. The emerging picture is one of diverse function, which implies differential regulation. Interestingly, the group I mGluRs are modulated by a rich variety of regulatory systems, which may explain how these receptors can mediate divergent actions when present in the same cell. J. Cell. Physiol. 191: 125–137, 2002. © 2002 Wiley-Liss, Inc.