The brain has long been considered an immunologically privileged site. Tissue transplanted to the central nervous system (CNS) is immunologically better tolerated than grafts to other regions of the body. With improved graft survival, tissue transplantation may provide new treatment options for previously incurable CNS disorders. The normal immune response is reviewed, followed by a discussion of the factors responsible for graft rejection. The modification of these factors to allow successful CNS transplantation is discussed.