Varicocele, the leading cause of male infertility, can impair spermatogenesis through several pathophysiological mechanisms. Of these, current evidence suggests that oxidative stress is the central element contributing to infertility in men with varicocele, to which the testis responds by way of heat stress, ischaemia or production of vasodilators, such as nitric oxide. Surgical varicocele repair (varicocelectomy) is beneficial not only for alleviating oxidative stress-associated infertility, but also for preventing and protecting against the progressive character of varicocele and its consequent upregulations of systemic oxidative stress. However, antioxidant therapy in infertile men with surgically treated and those with untreated varicocele is poorly studied, and well-designed trials are needed.