Aquaporin-1 (AQP1) water channels are expressed widely in microvascular endothelia outside of the central nervous system, including renal vasa recta and tumor microvessels, as well as in non-vascular endothelia in pleura, peritoneum, cornea, and lymphatics. In kidney, AQP1-facilitated water transport in outer medullary descending vasa recta is likely an important component of the urinary concentrating mechanism. However, in most vascular endothelia outside of kidney, it remains uncertain whether AQP1 expression and high water permeability are physiologically important. AQP1 in non-vascular endothelia at the inner corneal surface is involved in the maintenance of corneal transparency. Recently, a new role of AQP1 in endothelial cell migration was discovered in analyzing the cause of defective tumor angiogenesis in AQP1-deficient mice. AQP1 facilitates endothelial cell migration by a mechanism that may involve facilitated water transport across cell protrusions (lamellipodia). AQP1 inhibitors may thus have aquaretic and antiangiogenic activity.