The growth of solid tumors is dependent on their capacity to acquire blood supply. Therefore, much effort has been directed towards the development of anti-angiogenic agents which inhibit the process of neovascularization. More recently, it has become apparent that the targeted destruction of the established tumor vasculature represents a complementary avenue for growing therapeutic opportunities. This review provides evidence that vascular tumor targeting is an effective anti-tumor strategy in animal models. It further describes strategies for the identification of putative tumor vascular targets and discusses future prospects for vascular targeting applications in the clinical setting.