Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Increased incidence of CV events in CKD is related to the presence, besides traditional CV risk factors, of non-traditional CV risk factors associated to renal insufficiency, like anemia. The role of red blood cells (RBC) in uremia has been taken into account almost exclusively in relation to their reduced number. However, RBC in the uremic milieu can acquire several abnormalities which may jeopardize their properties. In this review, we report the main qualitative abnormalities of RBC and their potential pathophysiological role in the increased CV risk of uremic patient.