Because of correlations between cardiovascular disease, inflammation, and renal failure, many investigators are pursuing nontraditional risk factors and therapies in order to reduce cardiovascular morbidity and mortality in the end‐stage renal disease (ESRD) population. Despite the disappointing lack of clinical effects with antioxidative therapies seen in large studies of the general population, some studies suggest a diminished cardiovascular risk in individuals with renal failure. This expanding new line of evidence is promising as a method to help alleviate the more than 20‐fold increase in risk of cardiovascular events in the ESRD population. Most of the current available studies have evaluated laboratory or physiologic endpoints, such as endothelial function and measures of oxidative burden, and have evaluated relatively small numbers of patients. However, it is currently premature to initiate widespread clinical therapy with antioxidants. Further investigation in this area should be supported to see if reported benefits can be duplicated in more widespread study populations, and to more accurately define the most appropriate choice of therapy, mode of therapy, and dose.