Müller (radial glial) cells span the entire thickness of the retina, and contact and ensheath every type of neuronal cell body and process. This morphological relationship is reflected by a multitude of functional interactions between retinal neurons and Müller cells, including extracellular ion homeostasis and glutamate recycling by Müller cells. Virtually every disease of the retina is associated with a reactive Müller cell gliosis. Müller cell gliosis may either support the survival of retinal neurons or accelerate the progress of neuronal degeneration. Müller cells are key mediators of nerve cell protection, especially via release of basic fibroblast growth factor, via uptake and degradation of the excitotoxin glutamate, and via secretion of the antioxidant glutathione. Neovascularization during hypoxic conditions is mediated by Müller cells via release of vascular endothelial growth factor and transforming growth factor β or via direct contact to endothelial cells. Primary Müller cell insufficiency has been suggested to be the cause of different cases of retinal degeneration including hepatic and methanol-induced retinopathy and glaucoma. It is conceivable that, in the future, new therapeutic strategies may utilize Müller cells for, e.g., somatic gene therapy or transdifferentiation of retinal neurons from dedifferentiated Müller cells.