Immunoinfertility because of antisperm antibodies (ASA) is an important cause of infertility in humans. The incidence of ASA in infertile couples is 9–36% depending on the reporting center. Early claims regarding the incidence and involvement of ASA in involuntary infertility were probably overemphasized, which has resulted in subsequent confusion, doubt, and underestimation of their clinical significance. No immunoglobulin that binds to sperm should be called an antisperm antibody in a strict sense unless it is directed against a sperm antigen that plays a role in fertilization and fertility. ASA directed against the fertilization-related antigens are more relevant to infertility than the immunoglobulins that bind to sperm associated antigens. Several methods have been reported for treatment of immunoinfertility. These include: immunosuppressive therapies using corticosteroids or cyclosporine; assisted reproductive technologies such as intrauterine insemination, gamete intrafallopian transfer, in vitro fertilization, and intracytoplasmic sperm injection; laboratory techniques such as sperm washing, immunomagnetic sperm separation, proteolytic enzyme treatment, and use of immunobeads. Most of the available techniques have side effects, are invasive and expensive, have low efficacy, or provide conflicting results. Recent findings using defined sperm antigens that have a role in fertilization/fertility have provided animal models and innovative novel perspectives for studying the mechanism of immunoinfertility and possible modalities for treatment. The better understanding of local immunity and latest advances in hybridoma and recombinant technologies, proteomics and genomics leading to characterization of sperm antigens relevant to fertility will help to clarify the controversy and to establish the significance of ASA in infertility.