The field of antiangiogenesis has shown a remarkably rapid evolution from the discovery at the bench to translation into the clinic. Currently a wide variety of compounds are in clinical trial as inhibitors of angiogenesis, and new compounds are being frequently added. The target cell of most angiogenesis inhibitors is the endothelial cell, with inhibitors that selectively affect a number of endothelial cell functions acquired during angiogenesis, including activation, proliferation, migration, invasion and survival. The endothelial cell may also be targeted by chemotherapeutic agents currently in use. The high doses and intermittent treatment schedules used to fight resistant tumor cells may be altered towards lower doses and chronic administration to obtain selective inhibition of angiogenic factor-stimulated endothelial cells as adjuvant therapy. Finally, gene therapy is a promising route for the delivery of novel protein inhibitors of angiogenesis, and is actively being investigated.