Post-mortem histopathological studies report on reduced glial cell numbers in various frontolimbic areas of depressed patients implying that glial loss together with abnormal functioning could contribute to the pathophysiology of mood disorders. Astrocytes are regarded as the most abundant cell type in the brain and known for their housekeeping functions, but as recent developments suggest, they are also dynamic regulators of synaptogenesis, synaptic strength and stability and they control adult hippocampal neurogenesis. The primary aim of this review was to summarize the abundant experimental evidences demonstrating that antidepressant therapies have profound effect on astrocytes. Antidepressants modify astroglial physiology, morphology and by affecting gliogenesis they probably even regulate glial cell numbers. Antidepressants affect intracellular signaling pathways and gene expression of astrocytes, as well as the expression of receptors and the release of various trophic factors. We also assess the potential functional consequences of these changes on glutamate and glucose homeostasis and on synaptic communication between the neurons. We propose here a hypothesis that antidepressant treatment not only affects neurons, but also activates astrocytes, triggering them to carry out specific functions that result in the reactivation of cortical plasticity and can lead to the readjustment of abnormal neuronal networks. We argue here that these astrocyte specific changes are likely to contribute to the therapeutic effectiveness of the currently available antidepressant treatments and the better understanding of these cellular and molecular processes could help us to identify novel targets for the development of antidepressant drugs.