Los of renal function is associated with uremia-associated immune deficiency, which contributes significantly to the mortality and morbidity of end-stage renal disease (ESRD) patients. In this review, the effect of ESRD on the adaptive cellular immune system is discussed. Progressive loss of renal function causes a preferential loss of number and function of lymphoid cells. More in depth analysis of these changes reveals a loss of thymic function, attrition of telomeres, and expanded memory T cell population, which is compatible with the concept of premature immunological ageing. Latency for cytomegalovirus is associated with more profound changes and the expansion of a unique pro-inflammatory, cytotoxic subset of CD4-positive CD28null T cells. Epigenetically, modifications in hematopoietic stem cells may underlie uremia-associated immunological ageing, which is not reversed by kidney transplantation. Possible therapeutic options to reverse or halt uremia-associated immunological ageing are discussed.