Fertilization is a unique event in the life of an organism and results from requisite and reciprocal cell-induced sperm and egg activation events mediated by unique cellular and environmental cues associated with either the gametes or the reproductive tract/environment. Sperm interaction with the female reproductive tract/environment and sperm-egg interaction both at a distance and in close proximity represent a series of integrated processes designed to deliver sperm with optimal fertilizing potential to the site of fertilization. The idea that sperm and eggs "communicate" prior to fertilization, and that these communicative processes are requisite for successful fertilization, has been proposed for nearly a century. Recent studies have revealed that many aspects of gamete activation prior and subsequent to fertilization have similarities to intercellular and intracellular signaling systems utilized by somatic cells. The nature of these signaling systems is now being elucidated at the molecular level in both vertebrate and nonvertebrate systems and has revealed some unique aspects of communication and transmembrane signaling between gametes. This review will consider the mechanisms by which eggs communicate with sperm to initiate sperm activation events that are essential for fertilization. It will focus particularly on some of the most recent work surrounding these issues, and new directions and questions that are relevant to this most highly specialized interaction between gametes will be discussed.