Chronic kidney disease (CKD) is associated with a sharp increase in the risk for cardiovascular disease, which can only be partially explained by known classical risk factors. However, there is a well-established association with increased systemic inflammation. In the last decade, an unique cytotoxic CD4(+) T cell population has been identified, which can be recognized by the loss of the costimulatory cell surface marker CD28, hence their name CD4(+)CD28null T cells. These cells are highly proinflammatory, have the functional features of professional killer lymphocytes and can expand from less than 1% to over 50% of the total CD4(+) T cell population. In this review, we show that these cells probably play an important role in destabilizing atherosclerotic plaques and could explain, at least in part, the association of cardiovascular disease with an increased inflammatory milieu in CKD patients.