Aquaporins (AQPs) are small integral membrane proteins that provide a major pathway for water transport in many epithelial and endothelial cell types of several tissues. Aquaporin-4 (AQP4) is prevalently expressed in the brain and here we summarize data from our findings and from other literature concerning AQP4 expression in the cerebellum and the relationships between its expression and blood-brain barrier differentiation and integrity. The role of AQP4 in blood-brain barrier pathological conditions associated with an increased vascular permeability is also discussed. Overall, the data clearly indicate a close relationship between blood-brain barrier functioning and the control of water flux by astroglial cells and the crucial role played by AQP4 in this setting.