Brain injury leads to inflammation, stress, and cell death. Neurons are more susceptible to injury than astrocytes, as they have limited antioxidant capacity, and rely heavily on their metabolic coupling with astrocytes to combat oxidative stress. Both normally and after brain injury, astrocytes support neurons by providing antioxidant protection, substrates for neuronal metabolism, and glutamate clearance. Although astrocytes are generally more resilient than neurons after injury, severe damage also results in astrocyte dysfunction, leading to increased neuronal death. This mini review provides a very insightful and brief overview on a few examples of promising neuroprotective compounds targeting astrocyte function, with specific attention on how these treatments alter astrocyte response or viability, and how this may be critical for neuronal survival following brain injury. © 2012 Informa Healthcare USA, Inc.