Oxidative stress in the male germ line is thought to affect male fertility and impact upon normal embryonic development. Accordingly, fertility specialists are actively exploring the diagnosis of such stress in spermatozoa and evaluating the possible use of antioxidants to ameliorate this condition. In this review, evidence for the presence of oxidative stress in human spermatozoa, the origins of this phenomenon, its clinical significance in the aetiology of male infertility and recent advances in methods for its diagnosis and treatment are re-examined. Moreover, an extensive review of the results presented in published clinical studies has been conducted to evaluate the overall impact of oral antioxidants on measures of sperm oxidative stress and DNA damage. Administration of antioxidants to infertile men has been assessed in numerous clinical studies with at least 20 reports highlighting its effect on measures of oxidative stress in human spermatozoa. A qualitative but detailed review of the results revealed that 19 of the 20 studies conclusively showed a significant reduction relating to some measure of oxidative stress in these cells. Strong evidence also supports improved motility, particularly in asthenospermic patients. However, of these studies, only 10 reported pregnancy-related outcomes, with 6 reporting positive associations. Adequately powered, placebo-controlled comprehensive clinical trials are now required to establish a clear role for antioxidants in the prevention of oxidative stress in the male germ line, such that the clinical utility of this form of therapy becomes established once and for all.