Naturally-occurring antisperm antibodies in men are a relative cause of infertility, being the fertility impairment related with the degree of sperm autoimmunization. The impairment of sperm penetration through the cervical mucus represents the best established mechanism of the antibody interference with fertility. Another mechanism may involve complement-mediated sperm injury and opsonizing effect through the female genital tract. Finally, sperm-bound antibodies can interfere with sperm functions involved in the fertilization process, mainly in the sperm-zona pellucida interaction. While some mechanisms of the antibody-interference with fertility depend only on the degree of sperm autoimmunization (e.g., inhibition of cervical mucus penetration), other mechanisms (e.g., interference with gametes interaction) could or could not occur depending on the relevance in the fertilization process of the specific antigen(s) recognized by antisperm antibodies, which are policlonal in nature. Intrauterine insemination is an effective treatment when sperm autoimmunization is low or moderate, mainly if combined with corticosteroid treatment and superovulated cycles. On the contrary, its effectiveness in cases of high degree of sperm autoimmunization is controversial. The resort to "high tech" procedures is mandatory when other less invasive approaches have failed or they may also be chosen as a first-choice method in cases of high degree of sperm autoimmunization. Since in most reports the fertilization rate with in vitro fertilization and embryo transfer (IVF-ET) was significantly lower in the presence of sperm-bound antibodies than in the case of other indications, the likelihood of fertilization is higher with intracytoplasmatic sperm injection (ICSI), where the reported fertilization rates are similar to those in other indications, or even higher.