Investigating interactions of glia cells and synapses during development and in adulthood is the focus of several research programmes which aim at understanding the neurobiology of brain physiological and pathological processes. Both glia-specific released and membrane-bound proteins play essential roles in the development, maintenance and functionality of synaptic connections. Alterations in synaptic contacts in specific brain areas are hallmarks of several brain diseases, such as major depressive disorder, autism spectrum disorder and schizophrenia. Thus, a deeper knowledge about putative astrocyte dysfunctions which might affect the synaptic compartment is warranted to improve treatment options. Here, we present the latest advances about the role of glia cells in orchestrating the arrangement of synapses and neuronal networks in physiological and pathological states. We specifically focus on the role of astrocytes in the phagocytosis of neuronal synapses as a novel mechanism which drives the refinement of neuronal circuits and might be affected in pathological conditions. Finally, we propose this astrocyte-dependent mechanism as a putative alternative target of pharmacological interventions for the treatment of brain disorders.