Each day, the retina converts an immense number of photons into chemical signals that are then transported to higher order neural centers for interpretation. This process of photo transduction requires large quantities of cellular energy and anabolic precursors, making the retina one of the most metabolically active tissues in the body. With such a large metabolic demand, the retina is understandably sensitive to perturbations in perfusion and hypoxia. Indeed, retinal ischemia underlies many prevalent retinal disorders including diabetic retinopathy (DR), retinal vein occlusion (RVO), and retinopathy of prematurity (ROP). Retinal ischemia leads to the expression of growth factors, cytokines, and other cellular mediators which promote inflammation, vascular dysfunction, and ultimately, vision loss. This review aims to highlight the most recent and compelling findings that have advanced our understanding of the molecular mechanisms underlying retinal ischemias.