Glutamatergic signaling has been exceptionally well characterized in the brain's gray matter, where it underlies fast information processing, learning and memory, and also generates the neuronal damage that occurs in pathological conditions such as stroke. The role of glutamatergic signaling in the white matter, an area until recently thought to be devoid of synapses, is less well understood. Here we review what is known, and highlight what is not known, of glutamatergic signaling in the white matter. We focus on how glutamate is released, the location and properties of the receptors it acts on, the interacting molecules that may regulate trafficking or signaling of the receptors, the possible functional roles of glutamate in the white matter, and its pathological effects including the possibility of treating white matter disorders with glutamate receptor blockers.