Sperm-reactive antibodies (SpAb) are found attached to sperm, or present in serum or seminal fluid, in approximately 6% of men presenting with infertility. Data supports their pathophysiological role in some cases by the interference with sperm motility and/or sperm-egg interaction. The occurrence of SpAbs may follow disruption of either the cellular barrier separating sperm antigens from the immune system (e.g. testis trauma or obstruction to sperm outflow), or to dysregulation of normal immunosuppressive activities within the male reproductive tract. The epididymis is likely to be the key site of antibody generation, especially in the setting of obstruction. Detection methods are all based on the detection of Ig isotypes rather than specific antibody-antigen interactions, which limits their usefulness. Treatment options in the past (immunosuppression, intrauterine insemination, conventional in vitro fertilization) have been superceded by intracytoplasmic sperm injection (ICSI) which appears to circumvent all adverse effects of male SpAbs.