Calcium influx through ion channels located on the release face of the presynaptic nerve terminal gates the release of neurotransmitters by the fusion of the secretory vesicle and the discharge of its contents. Recently, several lines of research have indicated that the relationship between the Ca2+ channel and the release site might be more complex than dictated simply by its role as an ion conduit. The evidence suggests that the channel and the transmitter-release mechanism exist as a multimolecular entity and that this interaction has functional consequences, not only on the mechanisms and properties of transmitter release, but also on the behavior of the presynaptic Ca2+ channel itself.