Last years saw the development of anti-angiogenic strategies in the treatment of cancers. Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) is a new drug targeting αvβ3 and αvβ5 integrins thanks to a specific peptide called RGD sequence. Cilengitide acts in correlations between endothelial cells, tumor cells and extracellular matrix. The promising results obtained with Cilengitide in vitro, used alone or in combination with cytotoxic chemotherapy or ionizing radiations, could give many hopes especially for the treatment of cerebral tumors. Clinical trials are nowadays ongoing in this indication. The aim of this review is to take stock of the situation on the mechanisms of action of the integrin inhibitor Cilengitide (EMD121974; Merck KGaA, Darmstadt, Germany) with a focus on the first pre-clinical and clinical results.