Tumor angiogenesis is a complicated process that is regulated by numerous factors simultaneously and in a coordinated fashion. Angiogenic factors drive the process of neovascularization, but the initiation of angiogenesis involves priming of endothelial cells so that they will respond to mitogenic stimuli. The angiopoietins (Ang) -1 and -2 mediate endothelial cell stability through binding to their endothelial cell-specific receptor, Tie-2. Ang-1 leads to endothelial cell stability, and, in vivo, to an actual decrease in angiogenesis. This is likely due to its ability to enhance adhesion to the perivascular tissues. In contrast, Ang-2 leads to endothelial cell instability and may be an initiating factor in angiogenesis, priming endothelial cells for mitogenic signals. Thus, a novel antiangiogenic strategy may be one that leads to enhanced endothelial cell stability, thereby protecting endothelial cells from standard angiogenic stimuli. This may ultimately lead to tumor dormancy by transforming a rapidly growing tumor into an indolent tumor.