Anti-VEGF therapy appears to benefit patients with glioblastoma in part via its anti-edema mechanisms. The extent to which such edema reduction may benefit patients is not clear, either in terms of survival or neurological function. In a study of 30 patients treated with cediranib, imaging changes after one day of treatment correlated with progression-free and overall survival, and a “vascular normalization index” that combines imaging and blood biomarkers was highly correlated with these long-term outcomes. Imaging can assess a variety of mechanisms of anti-VEGF therapies, and one such imaging method is diffusion tensor imaging, a method particularly suited for visualizing white matter tracts and the edema which may surround and possibly impair them. The cover image shows diffusion tractography before (top) and four months after treatment with cediranib (bottom), with re-emergence of the white matter tracts clearly evident. The reduction in edema allows markedly improved visualization of frontal lobe white matter tracts; the direct functional significance of these changes remains to be elucidated, but cediranib and other anti-VEGF therapies have been reported to show increased overall survival in single-arm studies. Further mechanistic imaging and randomized trials are underway to better understand the potential benefit of these agents, as well as validate the predictive performance of the vascular normalization index. A movie of these data is available online through a Supplementary Data link from this article (doi: 10.1158/0008-5472.CAN-09-0814). For details, see the article by Sorensen and colleagues on page 5296 of this issue.