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Close to 38 500 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. Traditional therapy for SCCHN has involved a multimodality approach of radiotherapy, surgery, and chemotherapy. More recently, novel therapeutic targets for solid tumors, including SCCHN, have been subject to preclinical and clinical applications.One of these newer approaches is antiangiogenic therapy. The mechanism of angiogenesis and the role it plays in tumor growth has been the subject of extensive investigation over the last 3 decades. As new antiangiogenic agents are being approved for the treatment of various solid tumors this critical review, using current preclinical and clinical evidence available thus far, examines the possible future role this new modality will have in the management of SCCHN. The different steps of angiogenesis and the corresponding targets are discussed, with a focus on vascular endothelial growth factor, as well as the preclinical and clinical evidence for the role of angiogenesis in SCCHN.