Corneal graft rejection represents the leading cause of failure in corneal transplantation. Two of the major risk factors for graft rejection are previous sensitization, usually in the form of a previous rejected corneal graft and corneal vascularization. The major histocompatibility MHC antigens (HLA, A, B and DR) are the target of the corneal graft rejection process. Because HLA, A, B, and DR antigens have been found in the corneal epithelium, the corneal stroma, and the corneal endothelium, matching patients and donors would seem to reduce the incidence of rejection. The results of studies on HLA, A, B, and DR matching are discussed. Cyclosporin, a fungal by-product, prevents the proliferation of sensitized cytotoxic T cells. Its use topically in corneal transplant patients in a controlled series has also reduced the incidence of rejection. Its use systemically has also been tried in an effort to prevent corneal graft rejection.