Increasing evidence has demonstrated an astrocytic key role in the brain, namely in the modulation of synapses, neuronal networks, and behavior, proving that these are more than mere supportive cells. Indeed, astrocytes gained recognition as the third active element of a synapse. In this tripartite synapse concept, while interacting closely with neurons, these cells can modulate neuronal activity by sensing, processing, integrating, and responding to synaptic transmission. Astrocytes were shown to sense glutamate, the most abundant excitatory neurotransmitter in the brain, which occurs by activation of metabotropic glutamate receptor 5 (mGluR5). Activation of mGluR5 triggers Ca2+ elevations in astrocytes with consequences for synaptic function in cortico-limbic areas that are critical for cognitive processing. However, most of these studies were focused on the biological role of mGluR5 in young rodents, often using in vitro or ex vivo approaches. Therefore, the goal of this study was to understand better the impact of astrocytic mGluR5 in the cognitive processing of adult mice. Here, we induced the deletion of mGluR5 in astrocytes in adult mice and performed a full behavioral characterization. Our results revealed a novel role for mGluR5-mediated astrocytic modulation of mood and cognition, pointing out an important therapeutic potential for psychiatric disorders.