Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work-up of renal allograft dysfunction-an update. Curr Opin Nephrol Hypertens 8:723-728, 1999). A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the "drug level" era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients.