Exocytosis in neurones and neuroendocrine cells is triggered by an increase in the cytosolic concentration of Ca2+, and is followed by endocytotic membrane retrieval. Electrophysiological studies have characterized the nature of the Ca2+ signal that is required for exocytosis, and have defined the Ca(2+)-dependent steps in exocytotic and endocytotic vesicle cycling. In parallel, biochemical approaches have led to the discovery of a range of proteins that appears to function in synaptic- and secretory-vesicle dynamics. The nature of the Ca(2+)-binding proteins, and how they interact with the identified components of the exocytotic and endocytotic machinery, remain key unresolved issues. However, it is apparent that exocytosis involves multiple Ca(2+)-binding proteins with different affinities, and that the Ca2+ sensor involved in the final membrane-fusion step has different affinities for Ca2+ in synapses and neuroendocrine cells.