The glymphatic system is a recently discovered macroscopic waste clearance mechanism in the central nervous system (CNS) that utilizes perivascular channels formed by astrocytes to efficiently eliminate soluble proteins and metabolites. This system is primarily active during sleep and is largely inactive during wakefulness. The glymphatic system may also distribute non-waste compounds such as glucose, lipids, amino acids, and neurotransmitters. Recent studies indicate that glymphatic function is suppressed in various diseases, including neurodegenerative disorders, traumatic brain injury, and stroke, and that failure of this system might contribute to pathology. The review covers the basic structural elements, organization, regulation, and functions of the glymphatic system, highlighting its role in waste clearance and its potential implications for brain health and disease.The glymphatic system is a recently discovered macroscopic waste clearance mechanism in the central nervous system (CNS) that utilizes perivascular channels formed by astrocytes to efficiently eliminate soluble proteins and metabolites. This system is primarily active during sleep and is largely inactive during wakefulness. The glymphatic system may also distribute non-waste compounds such as glucose, lipids, amino acids, and neurotransmitters. Recent studies indicate that glymphatic function is suppressed in various diseases, including neurodegenerative disorders, traumatic brain injury, and stroke, and that failure of this system might contribute to pathology. The review covers the basic structural elements, organization, regulation, and functions of the glymphatic system, highlighting its role in waste clearance and its potential implications for brain health and disease.