Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. Following the conventional treatment, most patients with advanced HNSCC often face a considerable risk of locoregional disease recurrence, due to the occurrence of the resistance to therapy or of metastasis. Despite continued advances in the therapeutic options, the traditional therapies conducted in HNSCC to date have largely lacked efficacy or associated with significant toxicity. Angiogenesis plays an important role in HNSCC initiation and progression. Recently, targeted angiogenesis therapy draws a broad attention, because it can specifically enhance the efficacy of chemotherapy without an increased toxicity profile. Numerous ongoing preclinical studies and clinical trials exploring anti-angiogenetic inhibitors are being tested in HNSCC. Integration targeted angiogenesis therapy with the traditional modalities of surgery, radiotherapy, and cytotoxic chemotherapy for HNSCC might be a direction in the future. This review discussed current knowledge of the targeted angiogenesis therapies, recent development of anti-angiogenesis agents, and summaries of the clinical evaluation on use of these therapies for HNSCC.