The formation of new blood vessels (angiogenesis) is crucial for the growth and persistence of primary solid tumors and their metastases. Furthermore, angiogenesis is also required for metastatic dissemination, since an increase in vascular density will allow easier access of tumor cells to the circulation. Induction of angiogenesis precedes the formation of malignant tumors, and increased vascularization seems to correlate with the invasive properties of tumors and thus with the malignant tumor phenotype. In the last few years, the discovery and characterization of tumor-derived angiogenesis modulators greatly contributed to our understanding of how tumors regulate angiogenesis. However, although angiogenesis appears to be a rate-limiting event in tumor growth and metastatic dissemination, a direct connection between the induction of angiogenesis and the progression to tumor malignancy is less well understood. In this review, we discuss the most recent observations concerning the modulation of angiogenesis and their implications in tumor progression, as well as their potential impact on cancer therapy.