Axons are the physical conduits by which information is relayed within the nervous system and as such, are essential for normal neurological function. In the central nervous system (CNS), axons comprise the bulk of the white matter, where they are closely associated with glial cells. Primary alterations of glial cell functions can have detrimental secondary consequences for axons, demonstrating that white matter glia are important custodians of axonal integrity. For example, genetic ablation of key oligodendroglial molecules abrogates the oligodendrocytes’ supportive function, while expression of mutant super oxide dismutase in astrocytes expedites progression of motor neuron disease. Here we review some of the recent literature on the role of CNS glia in axonal health.