Enthusiasm for tolerance induction has been tempered by the realization that it is more difficult to achieve clinically than was predicted by experimental models. Unlike the view that the immune response to an allograft is ordered and thus predictable, we view alloimmunity as highly plastic and molded by previous and ongoing experiences with allogeneic and environmental antigens. This implies that an individual's response to an allograft changes over time and that responses of seemingly similar individuals may vary greatly. This variability highlights the need to develop assays for monitoring the recipient immune response as well as individualized methods for therapeutic immune modulation.