Corneal transplantation is the most common and successful type of allotransplantation surgery. Post-transplant immune response in keratoplasty is less pronounced than that in other transplantation procedures, which is accounted for by anatomical features of the cornea and, also, its low antigenic potential and active immunosuppression. However, the immune privilege of the cornea can be violated by neovascularization, inflammation, or trauma. Patients who require keratoplasty to restore their sight and whose immune privilege is disturbed, fall into a high-risk group and are likely to demonstrate tissue incompatibility and non-transparent engraftment. Two approaches exist as to how graft rejection can be prevented. One of them involves induction of donor-specific tolerance, the other — non-specific suppression of the recipient’s immune response. To avoid tissue incompatibility, measures can be taken to restore the immune privilege of the cornea as well as to induce antigen-specific tolerance, which is considered a promising, thought yet experimental, area of modern transplantology. In clinical practice, one pays most attention to improvement of non-specific immune suppression methods based on interfering in the metabolism of immunocompetent cells. Thus, timely prescriptions and proper immunosuppressive tactics with account to possible risk factors determine the outcome in high-risk patients undergoing corneal transplantation surgery.