Mammalian fertilization, a species-specific event, is the net result of a highly orchestrated process that collectively results in the fusion of two radically different-looking haploid cells, sperm and egg, to form a diploid zygote, a cell with somatic chromosome numbers. Prior to the interaction of the opposite gametes, mammalian spermatozoa undergo many fascinating changes during development in the testis, maturation in the epididymis, and capacitation in the female genital tract. Only the capacitated spermatozoa interact with the extracellular coat, the zona pellucida, which surrounds the mammalian oocyte. The tight and irreversible binding of the opposite gametes in the mouse and many other mammals studied, including human, starts a ca2+- dependent signal transduction pathway that results in the exocytosis of acrosomal contents at the site of the sperm binding. The hydrolytic action of the acrosomal glycohydrolases and proteinases, released at the site of the sperm-egg binding, along with the enhanced thrust generated by the hyperactivated spermatozoon, are important factors that regulate the penetration of the zona pellucida and fusion of the oppositegametes. The purpose of this editorial is to highlight the well programmed molecular events that are necessary before sperm-egg adhesion. In addition, my intention is to discuss the increasing controversy about the mechanism(s) that regulate mammalian sperm-egg interactions.