Free radicals are unstable molecules that have an unpaired electron in their last orbital, which makes them highly unstable agents. In medicine, it has been discovered that they play an important role in cell signaling and without them some cells such as leukocytes or sperm could not perform their biological functions. To protect itself from these oxidizing agents, the cell has a defense system based on antioxidants; however, when this balance is lost and oxidizing agents exceed the cellular antioxidant capacity, the cell enters oxidative stress, which affects cellular components such as proteins, nucleic acids, lipids, amino acids, and carbohydrates, among others. In the case of spermatozoa, due to their high metabolic rate, they produce large quantities of oxygen reactive species (ROS), decreasing sperm motility, alterations in cytoplasmic components, modifications in genetic material, or sperm death. In this chapter, a review is made of a brief history of how the toxicity of oxygen and free radicals was discovered, the oxidative stress in cells, and the effect of oxidative stress in the cytoplasmic sperm membrane, in the spermatic mitochondria, in the spermatic acrosome, in the sperm DNA, and in the fertility of the female and the male.