The induction of neoangiogenesis is a critical step already present at the early stages of tumor development and dissemination. The progressive identification of molecules playing a relevant role in neoangiogenesis has fostered the development of a wide variety of new selective agents. Antiangiogenic drugs should be integrated with conventional therapies; however, the design of the best sequence and timing for such combined treatments are still under investigation. In this review will be discussed the signal transduction mechanisms of angiogenic molecules, the development of specific inhibitors and their translation into clinical studies and, finally, the new perspectives in antiangiogenic therapy.