The glymphatic clearance pathway,) was described and named in 2013 as a system for waste clearance in the central nervous system (CNS) of vertebrates. Glymphatic flow was initially believed to be the complete answer to the long-standing question of how the sensitive neural tissue of the CNS functions in the perceived absence of a lymphatic drainage pathway for extracellular proteins, excess fluid, and metabolic waste products. The pathway consists of a para-arterial influx route for CSF to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal cord. Exchange of solutes between CSF and ISF is driven primarily by arterial pulsation and regulated during sleep by the expansion and contraction of brain extracellular space. Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ISF, facilitated by astrocytic aquaporin 4 (AQP4) water channels. The present-day literature reports that the glymphatic system is most active during slow wave sleep. Another key function of the glymphatic system was documented demonstrated that the brain’s system of perivascular pathways plays an important role in transporting small lipophilic molecules.