Treating cancer by targeting its vasculature is a recent conceptual revolution. It is now widely recognized that solid primary or disseminated tumor growth, as well as the process of blood vessel-mediated metastasis depend on the development of intra- and peri-tumoral vasculature. The rapid advance in the understanding of the process of vasculogenesis and angiogenesis has promoted the identification of a series of molecules that form a network controlling the formation, maturation and remodeling of vascular system. The use of newly discovered potent anti-angiogenic factors has confirmed the anti-growth and anti-metastatic efficiency of anti-angiogenic therapy in a variety of experimental solid tumor models. In addition, it appeared that such therapy with endostatin did not induce drug resistance allowing a repetitive long-term treatment. This review summarizes the biological basis of this new therapy, including antiangiogenic gene therapy, which open promising perspectives in cancer treatment.