Sleep is a naturally occurring physiological state that is required to sustain physical and mental health. Traditionally viewed as strictly regulated by top-down control mechanisms, sleep is now known to also originate locally. Glial cells are emerging as important contributors to the regulation of sleep-wake cycles, locally and among dedicated neural circuits. A few pioneering studies revealed that astrocytes and microglia may influence sleep pressure, duration as well as intensity, but the precise involvement of these two glial cells in the regulation of sleep remains to be fully addressed, across contexts of health and disease. In this overview article, we will first summarize the literature pertaining to the role of astrocytes and microglia in the regulation of sleep under normal physiological conditions. Afterward, we will discuss the beneficial and deleterious consequences of glia-mediated neuroinflammation, whether it is acute, or chronic and associated with brain diseases, on the regulation of sleep. Sleep disturbances are a main comorbidity in neurodegenerative diseases, and in several brain diseases that include pain, epilepsy, and cancer. Identifying the relationships between glia-mediated neuroinflammation, sleep-wake rhythm disruption and brain diseases may have important implications for the treatment of several disorders. © 2020 American Physiological Society. Compr Physiol 10:687-712, 2020.