Glial cells are increasingly recognized for their important interactions with both developing and mature neurons, in particular for maintenance of dendritic ramifications and spines, synapses, and neurotransmitter uptake. MicroRNA abnormalities are demonstrated in individual astrocytes with alterations in neurological diseases. Alexander disease is a prototype astrocytic disease because of genetically altered glial fibrillary acidic protein (GFAP) filaments. Other genetic diseases are now recognized as involving glial cells in their pathogenesis: Rett, Fragile-X, Aicardi-Goutières, and Down syndromes, as well as epigenetic effects in the mechanism of fetal alcohol spectrum disorder. Many involve glial production of cytokines and neuroinflammation. Microglia also may contribute. The heat-shock protein α-B-crystallin is expressed in the Rosenthal fibers of Alexander disease, in which the molecular structure of GFAP is altered, in astrocytes secreting neurotoxic cytokines, and focally at or near epileptic foci. Satellite glial cells adherent to neuronal soma are frequent and diagnostically nonspecific but may contribute to neuronal degeneration, especially of hypermetabolic epileptogenic neurons. Glial cells have distorted size and morphology in mTOR malformations. Failure of glial apoptosis in the fetal lamina terminalis is the likely pathogenesis of callosal agenesis and of other cerebral dysgeneses.