Regulated secretion is a fundamental cellular process in many different types of eukaryotic cells with Ca2(+-)triggered exocytosis taking centre stage. Elevations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) regulate multiple steps from vesicle fusion with the plasma membrane to fusion pore dilation and subsequent retrieval of spent vesicles. The general view is that the rise in [Ca(2+)](c) initiates during the pre-fusion stage and either results from Ca(2+)-influx via Ca(2+) channels in the plasma membrane or from release from intracellular Ca(2+)-stores. However, there is increasing evidence that exocytosis of secretory vesicles triggers additional, localised Ca(2+) signals via insertion of vesicle-associated Ca(2+) channels into the cell surface. These restricted Ca(2+) signals following fusion are ideally suited for regulating the post-fusion fate of individual secretory vesicles. In invertebrates they have been shown to trigger compensatory endocytosis. Recently we have reported that exocytosis of lamellar bodies in alveolar type II epithelial cells results in a localized Ca(2+)-influx via vesicular P2X(4) receptors which regulates fusion pore expansion and vesicle content release. This finding expands the emerging picture that post-fusion Ca(2+) entry via vesicle-associated Ca(2+) channels plays a central role for regulated exocytosis.