Drugs that prevent the binding of VEGF to its trans-membrane cognate receptors have revolutionized the treatment of the most important chorioretinal vascular disorders: exudative age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. Pegaptanib, which binds to VEGF165 and longer isoforms, ranibizumab and bevacizumab, which bind all VEGF-A isoforms, and aflibercept, which binds VEGF-A, VEGF-B, and placental growth factor, all bind VEGF165 with high affinity. The drugs have relatively long half-lives (7 to 10 days) after intravitreal depot injections and clinical durations of action that usually exceed 4 weeks. Plasma VEGF concentrations decrease after intravitreal injections of bevacizumab and aflibercept because their systemic half-lives are extended by their Fc fragments. Extensive in vitro and in vivo testing shows that the drugs prevent VEGF-mediated activation of endothelial cells while exhibiting little evidence of toxicity. Further anti-VEGF drug development is on-going.