The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect targeting by inhibiting the release of proangiogenic growth factors by cancer or stromal cells. Many patients benefit from antiangiogenic therapies; thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in their management. A number of non-invasive tools are described with their potential benefits and limitations. We review currently available candidate biomarkers of anti-angiogenic agent effect. Including these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, and prediction of individual response. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various other diseases.