Since the identification of several classes of receptor tyrosine kinases and their ligands as crucial mediators of vascular development, considerable progress has been made toward understanding the process of angiogenesis at sites of tissue growth and/or repair.(1,2) A number of clinical trials are currently evaluating angiogenic ligands for their ability to induce neovascularization in ischemic tissues 3,4 and the intracellular signaling pathways that mediate the proangiogenic effects of these growth factors are being extensively investigated. This review specifically focuses on the role of phosphatidylinositol-3 kinase (PI3K)-Akt signaling axis in endothelial cells because it is activated by many angiogenic growth factors and it regulates downstream target molecules that are potentially involved in blood vessel growth and homeostasis.