Sperm-egg interactions have been studied for many years using biochemical approaches such as the employment of antibodies and ligands that interact with sperm or with eggs and their vestments. As a result, various factors that participate in fertilization have emerged. However, when animals were genetically manipulated to examine the roles of those factors, most of them were found, to our surprise, to be "not essential". Of course, all biological systems contain redundancies and compensatory mechanisms, but at least some factors were found to be "essential" after gene disruption. As a whole, the explanations of sperm-egg interactions require significant modification from the gene manipulation point of view. In this review, information about sperm-egg interactions obtained from genetically manipulated animals is mainly revisited in order to propose a new vision.