We wish to comment on the recent publication by Katiski and Manes. We absolutely agree with the reviewers that there has been no consistent protective effect of any single antioxidant or combination against cardiovascular morbidity and mortality. However, one reason why antioxidant trials may have failed to show clinical benefit in these studies may be related to inappropriate patient selection. Thus, we would like to present a recent prospective double blind placebo controlled study (ICARE), which assessed potential cardiovascular benefit from vitamin E in a subgroup of patients with both Diabetes Mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype-agroup with very high oxidative stress. We believe that groups with evidence of a significant pro-oxidative and pro-inflammatory milieu such as the diabetic patients with the Hp 2-2 genotype, may benefit from antioxidants. Thus, better identification of such sub-groups, which will respond favorably to treatment with antioxidants is worthy of investigation.