Along with expanded knowledge of pathophysiological processes involved in transplant rejection, a variety of inummosuppressive agents with very specific modes of action have been developed. The focus of this review is an update on the pathophysiologic rationale and experience with such agents in human renal transplantation that are currently clinically available or are under investigation in human trials. Clinical data are reviewed with respect to calcineurin inhibitor sparing regimens based on mycophenolate or sirolimus, the use of leflunomide and its derivative FK778, modulation of chemotaxis with FTY720 or chemokine receptor blockers and the results of costimulatory blockade. While selection of one of these strategies may allow a more individualised therapy, the inummosuppressive potential of each compound has to be weighed against adverse reactions for an individual patient.