Tumor angiogenesis is one of the most prominent mechanisms driving tumor development and progression. In the past 30 years some of the most important signaling pathways linking specific angiogenic activities of tumor cells to fatal reactions of the patients vascular system have been elucidated. Crucial targets for therapeutic intervention have been identified and validated. Based on these achievements targeted drug development programs have been implemented to interfere with tumor angiogenesis as an attractive strategy in cancer treatment. The first targeted anti-angiogenic drugs have been approved for a variety of solid metastasizing cancers. Part 1 describes the basic mechanisms. Tumor-angiogenic signaling pathways are presented as new potential targets for anti-angiogenic therapy. Part 2 reviews the efforts made to validate new targets and to show efficacy in animals. Part 3 is devoted to the clinical development of the novel anti-angiogenic drugs and their use in clinical practice.