Organ transplantation has emerged from a few sporadic failed attempts to one of the most successful branches of surgery in the course of 50 years since the first identical twin transplant was performed in Boston. In this article I will attempt to portray the historical background and the recent shift of attitude regarding immunosuppression for solid organ transplants. Previously a culture of increasing immunosuppression and incorporating new and powerful agents into an already effective regimen has resulted in over-immunosuppression and more sepsis without an improvement in long-term graft survival. Over-immunosuppression is probably detrimental in preventing the natural control and "switching off" of the immune response as a vital function of the immune system and as a consequence any attempts to produce immunological tolerance are likely to be impaired by excessive immunosuppressive regimens. I will therefore explain and advocate a minimalistic approach to immunosuppression, a background on tissue typing and a summary of clinical results. Now that the procedure is perceived worldwide as an excellent therapy for previously doomed patients there is an increasing mismatch between the number of donor organs available and patients in need of a graft. This has produced ethical dilemmas previously unknown in the medical profession. These are extremely important considerations as they can undermine the Hippocratic tradition and the high ethical standing previously enjoyed by our profession.