Degenerative diseases of the retina afflict millions of Americans, and very few effective treatments are available at present. Transplantation of solid tissue or stem cell grafts represents a promising, albeit challenging, approach to replace photoreceptor cells lost due to injury or disease. However, there remain a number of formidable obstacles to be overcome before these techniques can be applied in a clinical setting. Foremost of these challenges is immunological acceptance and survival of the graft. We will refer to studies performed in collaboration with J. Wayne Streilein over the past decade that address this issue. The immune-privileged status of the subretinal space, as well as the inherent immune privilege of retinal pigment epithelium, neuronal retina and neural stem cells will be described. The goal of these studies is to gain a better understanding of the immunological properties of both the donor tissues and recipient graft site in retinal transplantation. This information will allow for the development of strategies to improve graft outcome and lead to successful repair of the diseased eye.