Mammalian sperm undergo discharge of a single, anterior secretory granule following their attachment to the zona pellucida surrounding the oocyte. This secretory discharge is known for historical reasons as the acrosome reaction. It fulfils a number of purposes and without it, sperm are unable to penetrate the zona pellucida and fuse with the oocyte. In this review, we focus on the role of the acrosome reaction in the development of fusion competence in sperm. Any naturally occurring membrane fusion has two (...) major sequential steps: a docking or adhesion step, in which two membranes adhere, and a fusion step, in which their lipid bilayers are destabilized and merged and a cellular compartment is either created or destroyed. Recent evidence suggests that there is an important role for oocyte integrins and sperm‐bound disintegrins in mammalian sperm/oocyte adhesion and fusion. The fusion mechanism employed by sperm remains poorly understood, however, and circumstantial evidence suggests it is more complex than the interaction between a single protein species and its target. Sperm/oocyte fusion is probably the most accessible eukaryotic model for intercellular fusion currently available, partly because it is temporally separated from gene expression. Elucidation of the mechanism of sperm/oocyte fusion may throw light on the mechanism of other intercellular fusions such as myoblast fusion, and the evolutionary relationship of intercellular membrane fusion to intracellular membrane fusion. (shrink)