Over the last decades, acrosomal exocytosis (also called the "acrosome reaction") has been recognized as playing an essential role in fertilization. Secretion of this granule is an absolute requirement for physiological fertilization. In recent years, the study of mammalian acrosomal exocytosis has yielded some major advances that challenge the long-held, general paradigms in the field. Principally, the idea that sperm must be acrosome-intact to bind to the zona pellucida of unfertilized eggs, based largely on in vitro fertilization studies of mouse oocytes denuded of the cumulus oophorus,...