Disorganized tumor vasculature leads to poor perfusion and hypoxia, both contributing to cytoxic treatment failure. The authors show that treatment of tumors with drugs that target EGFR-ras-PI3K-AKT signaling (STIs) improves vascular function. The image from a tumor treated with Nefinavir shows in blue the Hoechst dye indicating perfusion seen between the GFP labelled tumor cells and the red stained vessels. Quantitation of such images revealed that STI treatment improved blood flow, enhanced vascular maturation and eliminated hypoxia. This could create a new paradigm for the use of STIs to condition tumors for therapy with drugs or radiation. For details, see the article by Qayum and colleagues on page 6347 of this issue.