Vascular endothelial growth factor (VEGF) plays an important role in the pathophysiology of several sight-threatening retinal disorders such as age-related macular degeneration, diabetic macular edema and proliferative diabetic retinopathy. The discovery of anti-VEGF agents has revolutionized our treatment of these conditions. There are 4 anti-VEGF agents that are either approved or in common use in ophthalmology, namely pegaptanib (Macugen, Pfizer), ranibizumab (Lucentis, Novartis), aflibercept or VEGF Trap-Eye (EYLEA, Bayer) and bevacizumab (Avastin, Roche). There are differences between them. In this review, the differences are discussed in detail. Furthermore, an attempt is made to explain some of the clinical trial data based on their differences in ocular efficacy, duration of action, and local and systemic safety concerns.