Circulating donor-reactive effector memory T cells have been associated with allograft injury in humans. The next step to translate this observation into clinical practice is the design of clinical trials aimed at individualization of T cell-targeted therapy. The administration of immunosuppressive therapy based on the presence or absence of donor-reactive effector memory T cells could influence clinical outcomes, but independent of such therapy, when 'the persistence of memory' prevails, allograft injury may occur.