Glaucoma is a progressive optic neuropathy that has a multifactorial etiology. The most important risk factor is certainly an increased intraocular pressure. However, clinical observations have indicated that factors other than increased intraocular pressure also damage the neural tissue in glaucomatous optic neuropathy. The most prominent of these seems to be vascular dysregulation. Vascular tone is permanently regulated by a number of regulatory systems and factors, and the endothelial cell layer acts as an important mediator for the response to these factors. According to recent evidence, glaucomatous optic neuropathy may be associated with changes in endothelium-dependent vascular regulation. Consequently, therapeutic approaches based on vasodilator drugs acting via endothelium-derived substances are being developed. Although promising preliminary studies have been performed, the clinical relevance of such treatment remains to be clarified.