Abstract The discovery of the glymphatic system and meningeal lymphatic vessels revolutionized the understanding of brain waste clearance. These findings challenged the long-held notion of CNS immune privilege and provided insights into how the brain maintains homeostasis despite lacking conventional lymphatic drainage. However, the impact of pathological conditions, particularly CNS cancers, on the glymphatic system and vice versa remains underexplored. Glioblastoma (GBM) is the most common and aggressive primary adult CNS cancer. Its presence results in glymphatic dysfunction with significant clinical implications. Recent studies suggest that the glymphatic system interacts with GBM to influence immunity, drug delivery, fluid regulation and tumour progression, stressing its significant role in GBM biology and potentially treatment response. This review highlights the evidence for glymphatic dysfunction in GBM and its consequences. Furthermore, we discuss the potential to harness the power of the glymphatic system to improve patient outcomes in this terrible disease.