Sleep is vital and universal across all species studied, and lack of sleep has detrimental consequences for the organism. A broadly accepted theory for the purpose of sleep has yet to be defined. The discovery that sleep, but not wakefulness, allows removal of waste metabolites from the brain defines a new and interesting hypothesis for explaining the biological necessity for sleep: Sleep is for clearing the brain from the potential neurotoxic waste products that accumulate during wakefulness. Brain waste removal is driven by cerebrospinal fluid transport. We have denoted this pathway the ‘glymphatic system’ due to its functional resemblance with the lymphatic system in peripheral tissues and due to its dependence on glia. We here review recent developments focusing on the glymphatic system and sleep and suggest future studies that could shed new light on the reasons for the necessity of sleep for brain health.