Tumor angiogenesis, i.e. the formation of new blood vessels, is a promising therapeutic target. Whereas angiogenesis inhibitors (AI) are selectively aimed against the tumors' vascular system, irradiation targets both, tumor cells and tumor vasculature. Biological interaction of both modalities has been shown on the level of tumor endothelial cells and the microenvironment. The clinical testing of this novel combined treatment strategy so far has been hindered, because AI intuitively increase tumor hypoxia and hypoxic tumors are radio-resistant. However preclinical studies demonstrate that AI can even induce vascular normalization. Furthermore, consolidation therapy with AI after radiotherapy is a promising approach due to the specific biology of irradiated tumor bed. Based on these findings clinical studies are now increasingly been conducted.