Transcranial direct current stimulation (tDCS) has been reported to be effective in treating mood disorders such as major depressive disorder, however, its detailed mechanism of action is not fully understood. Human and animal experiments have demonstrated that tDCS promotes brain plasticity and have suggested that this consequence may underlie its therapeutic benefits. Nonetheless, the specific neurobiological underpinnings of tDCS-induced brain plasticity have only recently begun to be investigated. While brain plasticity occurs in synapses formed by neurons, astrocytes, a major glial cell type, have recently been shown to support synaptic plasticity via intracellular Ca signaling. In this perspective article, we discuss our recent results demonstrating that tDCS induces the activation of astrocytic calcium signaling that constitutes a required component for treating chronic restraint stress-induced depressive mice. We put forward the notion that activation of astrocytic Ca signaling could be used clinically as a potent remedy for depression.