The anti-angiogenic class of drugs is one of the few where representatives have gained international approval for clinical use in oncology during the past decade. Most of the biological and clinical activity of the currently available generation of anti-angiogenic drugs targets vascular endothelial growth factor (VEGF) and its related pathways. However, the clinical benefits associated with the use of these drugs have, so far, been limited. There is, therefore, an unmet need for biomarkers that can be used to identify patients who are most likely to benefit therapeutically and also to predict the best schedule and dosage for these drugs. Here, we discuss some of the emerging new combination strategies involving the approved anti-angiogenic drugs, some of the emerging targets associated with neoplastic angiogenesis and some novel agents used as a paradigm of the next generation of anti-angiogenic drugs. Copyright © 2011 Elsevier Ltd. All rights reserved.