Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinical outcomes (3 studies). The majority were small trials using a nonrandomized open-label design with a single HD group (no HD controls). Alpha-tocopherol was the most investigated antioxidant, with 20/25 studies reporting that this vitamin decreased oxidative stress, and one clinical outcome trial in 196 patients finding that it protected against secondary CVD. Studies using vitamin C were more equivocal, with 4/11 showing decreased oxidative stress and one clinical outcome trial showing no effect on morbidity or mortality. N-acetylcysteine was the most efficacious agent, with 4/4 studies indicating a decrease in oxidative stress and one trial (n=134) showing reduced CVD events. Seven studies have used therapy containing a combination of antioxidants, with five of these reporting decreased oxidative stress. Most intervention studies in HD patients, such as statin therapy and increased dialysis dose, have failed to show improvement in CVD outcomes. Two intervention trials using different antioxidants have found CVD benefits, suggesting that this line of therapy is effective in this resistant population. These studies require validation in larger, adequately powered trials.