In this review, I have summarised our understanding of acute rejection of organ transplants, and for convenience I have identified three processes, recognition, rejection and regulation. In stark contrast to this text-book picture of acute rejection, I have drawn attention to some of the clinical realities, where processes are altered by powerful immunosuppressive drugs, and where many transplant recipients are presensitised to transplantation antigens prior to engraftment. The ultimate goal is to encourage the emergence of a utopian immunological state, wherein patients tolerate organ transplants for life after being weaned from all immunosuppressive drugs. Assays that may be used in the future to reliably monitor this process are still at a very exciting stage of development. (C) 2005 Elsevier B.V All rights reserved.