The cross-talk between receptor tyrosine kinases and integrin receptors are known to be crucial for a number of cellular functions. On endothelial cells, an interaction between integrin α_vβ₃ and VEGFR2 seems to be particularly important process during vascularization. Importantly, the functional association between VEGFR2 and integrin α_vβ₃ is of reciprocal nature since each receptor is able to promote activation of its counterpart. This mutually beneficial relationship regulates a number of cellular activities involved in angiogenesis, including endothelial cell migration, survival and tube formation, and hematopoietic cell functions within vasculature. This article discusses several possible mechanisms reported by different labs which mediate formation of the complex between VEGFR-2 and α_vβ₃ on endothelial cells. The pathological consequences and regulatory events involved in this receptor cross-talk are also presented.