Purpose of review Altered differentiation and activation of T-cell subsets occur in patients with chronic kidney disease (CKD), but the impact on graft rejection and protective immunity during transplantation are not fully understood. Recent findings Patients with CKD have decreased frequency of naive T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naive and memory T-cell subsets do not appear to improve following kidney transplantation. Retained thymic output is associated with acute rejection, whereas naive lymphopenia and accumulation of CD8(+) TEMRA cells correlate with long-term graft dysfunction. CD28(null) memory cells accumulate during CKD and appear to confer protection against acute rejection under standard immunosuppression and possibly costimulation blockade. T cells bearing CD57 are also increased in patients with CKD and may underlie rejection during costimulation blockade. Summary The mechanisms by which CKD alters the differentiation and activation status of T-cell subsets is poorly understood. Further research is also needed to understand which cell populations mediate rejection under various immunosuppressive regimens. To date, there is little use of animal models of organ failure in transplant immunology research. CKD mouse models may help identify novel pathways and targets to better control alloimmunity in posttransplant.