Abstract: In recent years, both morbidity and mortality of chronic kidney disease （CKD） have been rising rapidly and cardiovascular disease （CVD） is one of major causes. Traditional cardiovascular risk factors cannot fully explain this phenomenon. Therefore such CKD-specific risk factors as uremic toxins （UTs） have emerged as crucial players. This review focused upon typical protein-binding toxin of indoxyl sulfate （IS）. It described the mechanisms of effects in the occurrence and development of CKD and depicted an association with IS and CKD-related CVD by four aspects of atherosclerosis, arteriosclerosis, congestive heart failure and arrhythmias. Also effective therapeutic measures of reducing serum level of IS were introduced, including restriction of protein intake, modulation of intestinal flora, using oral intestinal adsorbents and innovative dialysis approaches of enhancing IS clearance. And albumin-binding competitors appear to be an effective removal of protein-binding UTs. In the future, more modes of IS clearance shall be discovered and verified whether or not they can slow the progression of CKD and lower the incidence of CKD-related cardiovascular disease in CKD.