Mammalian sperm undergo discharge of a single, anterior secretory gran
ule following their attachment to the zona pellucida surrounding the o
ocyte. This secretory discharge is known for historical reasons as the
acrosome reaction. It fulfils a number of purposes and without it, sp
erm are unable to penetrate the zona pellucida and fuse with the oocyt
e. In this review, we focus on the role of the acrosome reaction in th
e development of fusion competence in sperm. Any naturally occurring m
embrane fusion has two major sequential steps: a docking or adhesion s
tep, 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 i
n mammalian sperm/oocyte adhesion and fusion. The fusion mechanism emp
loyed by sperm remains poorly understood, however, and circumstantial
evidence suggests it is more complex than the interaction between a si
ngle protein species and its target. Sperm/oocyte fusion is probably t
he most accessible eukaryotic model for intercellular fusion currently
available, partly because it is temporally separated from gene expres
sion. Elucidation of the mechanism of sperm/oocyte fusion may throw li
ght on the mechanism of other intercellular fusions such as myoblast f
usion, and the evolutionary relationship of intercellular membrane fus
ion to intracellular membrane fusion.