The glymphatic pathway is a fluid clearance system in the brain that facilitates the transport of cerebrospinal fluid (CSF) and interstitial fluid (ISF) through perivascular spaces, involving aquaporin-4 (AQP4) water channels. This pathway is primarily active during sleep, enhancing the clearance of harmful metabolites like amyloid-beta (Aβ) in rodents. Dysfunction of the glymphatic pathway has been observed in animal models of traumatic brain injury (TBI), Alzheimer’s disease (AD), and micro-infarct disease, often linked to altered AQP4 expression. Recent studies suggest that similar glymphatic pathways exist in humans, with MRI and PET imaging revealing CSF flow patterns and Aβ accumulation, indicating that the human glymphatic pathway may also be active during sleep. Reduced CSF clearance is associated with increased Aβ levels in AD patients. AQP4 expression is altered in AD and normal pressure hydrocephalus (NPH) patients, with reduced CSF tracer entry and clearance observed in NPH patients. Future research aims to confirm if glymphatic flow mechanisms in rodents apply to humans, evaluate CSF dynamics in humans, and assess glymphatic function after stroke or TBI. Understanding how behavior and genetics influence glymphatic function could lead to new diagnostic and therapeutic tools. The glymphatic pathway plays a crucial role in brain clearance, and its dysfunction is linked to neurodegenerative diseases. Studies in rodents and humans have shown that glymphatic function is affected by factors such as sleep, body posture, and physical exercise. Impaired glymphatic function is also associated with vascular dementia and other neurological conditions. Research continues to explore the glymphatic pathway's role in health and disease, with potential implications for the development of new treatments and diagnostic methods.The glymphatic pathway is a fluid clearance system in the brain that facilitates the transport of cerebrospinal fluid (CSF) and interstitial fluid (ISF) through perivascular spaces, involving aquaporin-4 (AQP4) water channels. This pathway is primarily active during sleep, enhancing the clearance of harmful metabolites like amyloid-beta (Aβ) in rodents. Dysfunction of the glymphatic pathway has been observed in animal models of traumatic brain injury (TBI), Alzheimer’s disease (AD), and micro-infarct disease, often linked to altered AQP4 expression. Recent studies suggest that similar glymphatic pathways exist in humans, with MRI and PET imaging revealing CSF flow patterns and Aβ accumulation, indicating that the human glymphatic pathway may also be active during sleep. Reduced CSF clearance is associated with increased Aβ levels in AD patients. AQP4 expression is altered in AD and normal pressure hydrocephalus (NPH) patients, with reduced CSF tracer entry and clearance observed in NPH patients. Future research aims to confirm if glymphatic flow mechanisms in rodents apply to humans, evaluate CSF dynamics in humans, and assess glymphatic function after stroke or TBI. Understanding how behavior and genetics influence glymphatic function could lead to new diagnostic and therapeutic tools. The glymphatic pathway plays a crucial role in brain clearance, and its dysfunction is linked to neurodegenerative diseases. Studies in rodents and humans have shown that glymphatic function is affected by factors such as sleep, body posture, and physical exercise. Impaired glymphatic function is also associated with vascular dementia and other neurological conditions. Research continues to explore the glymphatic pathway's role in health and disease, with potential implications for the development of new treatments and diagnostic methods.