Targeting the tumor vasculature to “starve a tumor to death” instead of targeting tumor cells with chemotherapeutic drugs was conceived over four decades ago and has led to the development of antiangiogenic drugs approved for use against various human malignancies . So far, however, antiangiogenic therapy has not fulfilled expectations because it aids only a subset of cancer patients and provides only transitory improvements. Vascular-disrupting agents were developed to more rigorously deplete tumor vessels . However, this approach leads to hypoxia, which promotes neovascularization and tumor regrowth. The sobering realization is that the more we try to exterminate tumor vessels, the more aggressively tumors respond to impede these efforts, sometimes becoming more belligerent tumors. Is manipulating the vasculature to control tumor growth a promising strategy after all?