Immune-mediated rejection of donor tissues is one of the largest challenges in transplant biology. While routine biopsy to monitor transplanted organs can be informative, this procedure is invasive and carries several risks. In this episode, Prashanth Vallabhajosyula and colleagues evaluated changes in transplant-derived exosomes in murine models and human transplant recipients. Their work indicates that changes in donor-derived exosomes can be used to noninvasively monitor transplant rejection.