Infertility affects approximately a quarter of all couples. Of these cases, roughly half are due to male factors. However, more than 50% of the causes of male factor infertility are still obscure. Contemporary Andrology includes a thorough analysis of the sperm looking at the cellular and subcellular imperfections which may have an adverse effect on fertility. Defects in DNA and chromatin structure are examples of such analysis. The structure of spermatozoa DNA is very unique, highly specialized in order to control time-appropriate maturation of the zygote. Damage to sperm DNA may occur as a result of intrinsic factors such as limited defenses against oxidative stress, ageing and varicocele, or as a result of extrinsic determinants such as medications and environmental factors. This damage thereby may have negative effects on ART procedures, and could lead to failure of fertilization. Sperm DNA damage significantly contributes to the growing number of infertility cases, and should be a part of a modern andrology lab.