The evaluation of anti-rejection treatments raises a variety of methodological problems depending on the clinical phase of development. The first administrations in man are carried out in order to study the profile of a drug and are sometimes performed in healthy volunteers, but more frequently in transplanted patients. It is then necessary to select and evaluate the assessment criteria which will be used in comparative studies to demonstrate the efficacy and safety of the new treatments compared with reference drugs. Factors responsible for variation may be related to the nature of the organ transplanted, the clinical condition of the donor and host and their immune compatibilities. Associated treatments and the multidisciplinary environment in which an organ transplant takes place should also be taken into consideration. After registration, knowledge about the new anti-rejection drug continues in order to identify the optimum conditions for its use, its true therapeutic efficacy and to determine possible new indications.