Varicocele is recognized as the leading cause of male infertility because it can impair spermatogenesis through several distinct pathophysiological mechanisms. Current evidence supports oxidative stress as a key element in the pathophysiology of varicocele-related infertility, although these mechanisms have not yet been fully described. Measurement of the reactive oxygen species and other markers of oxidative stress, including the levels of the antioxidant enzymes catalase and superoxide dismutase, can provide valuable information on the extent of oxidative stress and might guide therapeutic management strategies. The testis can respond to varicocele-associated cell stressors, such as heat stress, ischaemia or production of vasodilators (for example, nitric oxide) at the expense of the generation of excessive reactive oxygen species. These responses have their own implications in exacerbating the underlying oxidative stress and on the subsequent infertility.