Astrocytes or astroglia are heterogeneous cells, similar to neurons, that have different properties in different brain regions. The implications of steroid hormones on glial cells and stress-related pathologies have been studied previously. Glucocorticoids (GCs) that are released in response to stress have been shown to be deleterious to neurons in various brain regions. Further, in the light of the effect of GCs on astrocytes, several reports have shown the crucial role of glia. Still, much remains to be done to understand the stress-astrocytes-glucocorticoid interactions associated with the pathological consequences of various CNS disorders. This review is an attempt to summarize the effects of GCs and stress on astrocytes and its implications in depression.