Astroglia encompass a subset of versatile glial cells that fulfill a major homeostatic role in the mammalian brain. Since any brain disease results from failure in brain homeostasis, astroglial cells are involved in many, if not all, aspects of neurological and/or psychiatric disorders. In this article, the roles of astrocytes as homeostatic cells in healthy and diseased brains are surveyed. These cells can mount the defence response to the insult of the brain, astrogliosis, when and where they display hypertrophy. Interestingly, astrocytes can alternatively display atrophy in some pathological conditions. Various pathologies, including Alexander and Alzheimer's diseases, amyotrophic lateral sclerosis, stroke and epilepsy, to mention a few, are discussed. Astrocytes could represent a novel target for medical intervention in the treatment of brain disorders. © 2013 Future Medicine Ltd.