Tumor growth and metastasis depend on its angiogenesis ability. The anti-angiogenic treatment is considered as a hopeful treatment for tumors. The anti-angiogenic efficacy of classic cytotoxic agents, such as cyclophosphomide, methotraxate, taxol, and so on, could be enhanced by changing the dose delivering schedule, naming "metronomic chemotherapy". Additionally, tumor vasculature and hypoxic status are important predictive factors for the efficacy of radiotherapy. Furthermore, the anti-angiogenic treatment can enhance the irradiation sensitivity of tumors. This review have summarized the anti-angiogenic mechanism of metronomic chemotherapy combined radiotherapy and the preliminary applications in clinic and proposed that the combination of radiotherapy and metronomic chemotherapy can overcome the hypoxia-related radioresistance and increase the efficacy of radiotherapy.