Tumor-induced angiogenic blood vessels (tumor neovasculature) permit tumor survival, growth and metastasis. Compelling evidence supports the notion that the tumor neovasculature expresses specific molecular markers that are absent in the parental quiescent preformed blood vessels and can be exploited for molecular therapeutics. Therefore, the clinical success of selective killing of tumor neovasculature depends upon the identification of antigens that are specifically expressed by the tumor neovasculature, but not by preformed quiescent blood vessels. Many laboratories have identified, discovered and characterized the cellular and molecular components necessary to tumor-induced angiogenesis. This has led to the understanding of requisite interactions between endothelium, angiogenic cytokines, stromal cells, the supporting extracellular matrix molecules and proteases that accompany these processes. Notably, in the last ten years the signaling pathways mediated by angiopoietin, basic fibroblast growth factor and vascular endothelial growth factor, and in particular how they may promote formation tumor neovasculature, have been investigated in vitro and in vivo expeditiously. An in-depth understanding of tumor neovasculature-specific antigen clearly holds promises in the development of novel therapeutic strategies to treat aggressive cancers. A precision-based molecular therapy would be one that destroys the tumor neovasculature selectively, avoids toxicity and leaves parental vessels unharmed.