Current attempts to disrupt the complex process of tumor blood vessel formation are predominantly focused on targeting the vascular endothelial growth factor (VEGF)-VEGFR signaling pathway. Although clinically proven to inhibit VEGF and its receptors, these pharmacologic agents are selective, but not specific. Consequently, many of the approved inhibitors also impair other molecular targets leading to increased toxicity. Current efforts to unravel the complexity of tumor angiogenesis have identified several new candidates for antivascular therapy. In this review article, we identify well-established and novel angiogenic molecules and discuss benefits of the therapeutic approaches based on targeting of such factors.