"Wet" (also called neovascular) age-related macular degeneration (AMD) is a chronic progressive disease characterized by leakage of fluid or blood from choroidal neovascularization. It remains the leading cause of blindness in the developed world. Vascular endothelial growth factor (VEGF), which plays a key role in the pathogenesis of retinal neovascularization and vessel leakage leading to central vision loss, has emerged as a potential target in the treatment of wet AMD. Importantly, large-scale clinical trials have demonstrated that intravitreal VEGF antagonism prevents vision loss and may even improve visual acuity in patients with neovascular AMD. Because VEGF and its downstream mediator nitric oxide have a well-established cardioprotective role, however, it can be argued that the beneficial effects of VEGF antagonism in the eye may come at the cost of adverse systemic effects, particularly myocardial infarction and stroke.