The male factor appears to be responsible for 30%–50% of infertility. There are many causes of male subfertility, which can be traced back to congenital, acquired, or idiopathic factors. This chapter deals first with the relationship between oxidative stress and spermatozoa, then with some of the most frequent factors affecting male fertility. The factors include varicocele, urogenital infections, inflammation, obesity, genetic factors, pollutants, and lifestyle. Recently, it has been suggested that the spermatozoon accumulates epigenetic errors because of the constant mitotic and meiotic cycles during the spermatogenetic process. A better knowledge of the molecular and genetic factors involved in pathological reproductive conditions allows a deep investigation into the etiology of male factor infertility and a possible improvement of patients’ chances of reproductive success.