Despite the rapid development of new pharmacological and surgical modalities, the treatment of retinal disease all too often results in poor final visual acuity. The primary pathologic mechanism underlying suboptimal visual acuity following retinal disease is cell death. It is induced by a variety of stimuli including ischemia, inflammation, and oxidative stress. New neuroprotective strategies have recently being examined for the prevention of retinal cell death, yet there is still a need for pharmacological agents that are efficacious and lack adverse effects. These could possibly be employed alone or in combination with disease-specific treatments. The neuropeptide somatostatin and its sst2 receptor selective analogues have been shown to inhibit the ischemia-induced neovascularization in models of retinal ischemia, and to protect from ischemia-induced cell death. The aim of this review is threefold: a) to address the functional role of somatostatin and its receptors in retinal circuitry, b) to present recent evidence supporting the neuroprotective role of somatostatin in experimental models of retinal disease and c) to present the clinical studies that have been performed to date and support the use of somatostatin and its analogues as therapeutics in ophthalmology.