α5β1-integrins play a key role in angiogenesis, the formation of new vessels in tissues that lack them. By serving as receptors for a variety of extracellular matrix proteins containing an arginine-glycine-aspartic acid (RGD) sequence, these integrins mediate migration of endothelial cells into the basement membrane and regulate their growth, survival, and differentiation. Besides being involved in angiogenesis, the αvβ3-integrin is also presented on tumor cells of various origin, where it is involved in the processes that govern metastasis. Because the αvβ3-integrin is an attractive target for cancer treatment, high-affinity ligands containing the RGD sequence, for example, cyclic pentapeptides, have been developed. They inhibit angiogenesis, induce endothelial apoptosis, decrease tumor growth, and reduce invasiveness and spread of metastasis. This development finally resulted in cyclo(RGDf(NMe)V) (cilengitide), which is a drug for the treatment of glioblastoma (currently in phase III clinical trials).