A group of angiogenic signaling nodes that are of increasing interest as targets for antiangiogenic drug development, are reviewed. Angiogenesis is one of the several processes that form new blood vessels in higher animals. VEGF-A, a critical autocrine factor for maintaining endothelial function in the adult, has attracted the most attention as a molecular target for inhibiting tumor angionesis. One way to approach the problem for cancer therapy is to study how angiogenesis is normally controlled during developments and in adults and how this process becomes deregulated in nonmalignant disease. Nitric Oxides (NO) signaling plays an important role in the cardiovascular system that may be crucial to developing more effective therapeutic angiogenesis inhibitors. It is required that both the pharmacologically control pathologic angiogenesis targets should be defined and all the molecules should be combined into a signaling network.