Gliomas are characterized by very high levels of neo-vascularization holding out the hope that therapies aimed at angiogenesis will have a significant impact on this intractable family of tumors. Intense research into the molecular mechanisms that drive the formation of new blood vessels in response to tumor growth has revealed a great deal of complexity, at the heart of which are competing pro- and anti-angiogenic influences. The relevant signaling pathways, and how they might be manipulated to interfere in the promotion of vessel growth are discussed. Several types of anti-angiogenic lead compounds are already in clinical trials, but assessing their impact on brain tumors is not straightforward. We discuss in depth some of the practical aspects of using imaging to more meaningfully follow tumor progression and response to treatment, which is particularly relevant to the use of therapies that target blood flow directly, which is fundamental to modern imaging modalities.