Defective sperm function is the largest single defined cause of male infertility. In around one third of such cases, the etiology is thought to involve oxidative stress precipitated by excessive exposure to reactive oxygen/nitrogen species (ROS/RNS), often coupled with a reduction in seminal antioxidant protection. Spermatozoa are vulnerable to such stress because: (i) they possess very little cytoplasm in which to house the antioxidant systems that protect most cell types from oxidative damage, (ii) they possess abundant targets for ROS/RNS attack including high concentrations of polyunsaturated fatty acid, cysteine-rich proteins and nucleic acids, (iii) they are active generators of ROS/RNS using a variety of sources including the mitochondrial electron transport chain, NADPH oxidases and nitric oxide synthases. Critically, these cells live their lives on a redox knife-edge. Low levels of ROS production promote several important biological events including chromatin condensation, capacitation and acrosomal exocytosis. However, the continued generation of ROS eventually overwhelms these cells’ meagre antioxidant defenses, inducing a state of oxidative stress characterized by lipid peroxidation, DNA fragmentation, loss of functionality, senescence and, ultimately, programed cell death. Antioxidants have the potential to relieve such stress, however we still lack simple diagnostic procedures to select appropriate patients for treatment.