Vascular targeting is distinct from inhibition of angiogenesis, which aims at inhibiting tumor growth and inducing regression by destruction of the tumor vasculature. A fundamental principle of this approach is that tumor vasculature is different from that in normal tissues. The interest in vascular-targeted anticancer therapy arises from the dependence of tumor cells on a functional blood vessel system for survival, proliferation and metastatic dissemination. Hence, the possibility to indirectly inhibit tumor growth and survival by impairing neovessel formation or function. Vascular targeting agents impair the integrity and functionality of tumor vessels, leading to shutdown of the tumor vascular system and consequent tumor cell death. This article reviews recent studies on the use of specific vascular targeting agents and suggests that targeting of the vasculature of diseased organs could underlie a new pharmacological approach to the treatment of malignancies.