Astrocytes have not been a major therapeutic target for the treatment of stroke, with most research emphasis on the neuron. Given the essential role that astrocytes play in maintaining physiological function of the central nervous system and the very rapid and sensitive reaction astrocytes have in response to cerebral injury or ischemic insult, we propose to replace the neurocentric view for treatment with a more nuanced astrocytic centered approach. In addition, after decades of effort in attempting to develop neuroprotective therapies, which target reduction of the ischemic lesion, there are no effective clinical treatments for stroke, aside from thrombolysis with tissue plasminogen activator, which is used in a small minority of patients. A more promising therapeutic approach, which may affect nearly all stroke patients, may be in promoting endogenous restorative mechanisms, which enhance neurological recovery. A focus of efforts in stimulating recovery post stroke is the use of exogenously administered cells. The present review focuses on the role of the astrocyte in mediating the brain network, brain plasticity, and neurological recovery post stroke. As a model to describe the interaction of a restorative cell‐based therapy with astrocytes, which drives recovery from stroke, we specifically highlight the subacute treatment of stroke with multipotent mesenchymal stromal cell therapy. GLIA 2013;62:1–16