Advances in transplantation biology have greatly improved patient outcomes following transplant surgery. However, generalized immunosuppression remains the Achilles heel of modern transplantation surgery with its associated infectious and neoplastic morbidities. Tolerance remains the ultimate goal for the entire field. Although recent advances in transplant immunology suggest that tolerance may be achievable in the near future, the complex and redundant nature of the human immune system may not allow us to circumvent such a basic function as the recognition of nonself. In this paper, advances in transplant immunology are reviewed and their potential relevance to achieving the "Holy Grail" of transplantation are discussed.