Aquaporin-4 (AQP4) is the most important member of the aquaporin (AQP) family in the central nervous system and has a key role in maintaining water and ion homeostasis. It is clear that AQP4 participates in brain edema after injury and other brain diseases. Various studies report that AQP4 is significantly up-regulated in glioblastoma multiforme compared to low-grade glioma and normal brain tissue, suggesting that it might be involved in tumor malignancy as well as regulation of brain edema. Recent discoveries of AQP4 involvement in cell migration and cytoskeleton organization suggest that AQP4 has a critical role in glioma malignancy. This review focuses on the newly discovered functions and molecular mechanisms of AQP4 in infiltrative gliomas.