The principal classes of glia in the mature brain are astrocytes, microglia and oligodendrocytes. According to the Benington-Heller hypothesis, astrocytic glycogen, which acts as a reserve glucose store for neurons, is depleted during wakefulness and restored during non-rapid-eye-movement (NREM) sleep. Cerebral microglia and oligodendrocytes cells secrete a number of substances in vitro known to influence sleep or brain activity in sleep. As sleep deprivation is associated with an increase in markers of cellular stress, it has been proposed that substances secreted by microglia may play a central role in sleep regulation. An important future area of investigation is to determine the anatomic locations where glial cells exert their effects on sleep and/or brain activity. Glia is dispersed widely in subcortical and cortical brain areas including regions known to trigger sleep and wakefulness. Astrocytic adenosine is likely to be a key mediator of sleep behavior and brain activity.