Glaucoma is a frequent eye disease in the elderly and the second leading cause of irreversible blindness both in developed and developing countries (Resnikoff et al. 2004). Presently, about 50 million people are blind from glaucoma worldwide, a number that has not significantly changed over the last decade (Resnikoff et al. 2004; Thylefors et al. 1995). Without a doubt, glaucoma remains an unsolved problem of high significance in ophthalmology. Glaucoma is characterized by a chronic, progressive optic neuropathy that occurs in parallel to the formation of a typical excavation of the optic nerve head. The primary damage is restricted to retinal ganglion cells and the location of initial damage appears to be at the optic disc where their axons exit the eye. For a long time, intraocular pressure (IOP) had been suspected to cause or to contribute to axonal damage in glaucoma and since Adolph Weber introduced pilocarpine as an IOP-lowering therapy in 1876 (Weber 1876), medical therapy of glaucoma has been aimed at reducing IOP. This concept was challenged more recently, because of the observation that a significant percentage (up to 30–50 %) of patients suffering from glaucomatous neurodegeneration (Shiose et al. 1991; Anderson 2003) have IOPs in the statistically normal range of 10–21 mmHg (mean±2SD: 15.5±5.5 mmHg). Evidence for a causative or contributing role of IOP has finally been obtained through a number of randomized prospective multi-center studies that clearly identified IOP as the major risk factor for the pathogenesis of glaucoma (Collaborative Normal-Tension Glaucoma Study Group 1998a, b; Gordon et al. 2002; Kass et al. 2002; Leske et al. 2003; The AGIS Investigators 2000). Apparently, therapy that reduces IOP in patients with glaucoma is neuroprotective in the sense that it delays the structural and functional damage of retinal ganglion cell perikarya and their axons. Still, compliance to medical therapy is often unsatisfactory as daily eye-drop application is required (Reardon et al. 2011; Sleath et al. 2011). Although most patients are first treated with medical therapy, IOP-lowering operations come into play when medical therapy is no longer efficient, or when the patient is incompliant or does not tolerate topical eye drops. Presently, a large array of surgeries is available, all of which try to provide IOP reduction more than medical therapy can achieve with minimal surgical side effects. The advantage of the most effective surgical procedures is that very low IOPs (approx. 10–12 mmHg) can be achieved. In this respect, glaucoma surgery is the strongest neuroprotective measure on the basis of IOP lowering. However, surgery in glaucoma may not be successful, because of surgical complications and inappropriate wound healing. Moreover, there are only a limited number of randomized clinical trials assessing the success of surgical procedures in glaucoma (Coleman 2012). Considering the current limits of glaucoma therapy, there is need for the development of novel and alternative treatment strategies that save retinal neurons from glaucomatous injury or have the potential to repair neurons that have already been damaged. This Special Issue is aimed at providing a synopsis of therapeutically strategies with the potential to act neuroprotectively in glaucoma and independently from the reduction of IOP. Another purpose of the Special Issue is to review the obstacles that make the translation of experimental neuroprotective therapies into clinical practice E. R. Tamm (*) Institute of Human Anatomy and Embryology, University of Regensburg, Universitatstr. 31, 93053 Regensburg, Germany e-mail: Ernst.Tamm@vkl.uni-regensburg.de