There is growing appreciation for astrocytes as essential partners in the central response to stress. Insight from post-mortem human brain tissue has revealed extensive astrocyte remodeling in people who suffered from psychiatric disorders including major depressive disorder. Rodent models of stress disorders align with human data, showing that astrocyte dysfunction directly contributes to cellular and behavioral maladaptation following intense or chronic stress. Despite these links, more research is required to determine astrocyte-specific stress signalling mechanisms and whether these pathways can be targeted in a therapeutic strategy. Here, we detail an early-life stress paradigm that induces lifelong stress susceptibility associated with astrocyte dysfunction. In addition, we provide a detailed guideline to validate a stress model.