The cell-cell interactions that occur between sperm and egg involve not only the binding but also the fusion of the gamete plasma membranes. Numerous studies, carried out decades ago and more recently, have implicated several different molecules on both the sperm and egg as being involved in gamete membrane interactions. The sperm proteins that have received the most attention recently have homology to disintegrins, which are proteins in snake venoms that can interact with integrins. These sperm disintegrin-like proteins are members of a molecular family, known as ADAM's (for A Disintegrin and A Metalloprotease) or MDC's (for Metalloprotease, Disintegrin, Cysteine-rich). This review will focus on the molecules that have been implicated in mediating mammalian sperm-egg binding or the fusion of the gamete membranes. The molecules that will be discussed include three members of the ADAM/MDC family on sperm (fertilin alpha, fertilin beta, and cyritestin), integrins on eggs (alpha-6/beta-1 and others), and a number of other egg and sperm molecules, novel and characterized in other systems, that have been implicated in these processes.