Regulated exocytosis forms the basis for many intercellular signaling processes, for example, in hormone secretion or neurotransmitter release. During regulated exocytosis, the membrane of a secretory vesicle fuses with the plasma membrane in a tightly controlled reaction that is most often triggered by calcium. Recent advances have allowed major insights into the molecular mechanisms that mediate regulated exocytosis. In the present review, we will briefly discuss two key features of regulated exocytosis that have been particularly well studied recently. First, we will examine the current understanding of the membrane fusion reaction that underlies regulated exocytosis and that is effected by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) and munc18-like proteins similar to other membrane fusion reactions. Second, we will describe the role of the major candidates for the calcium sensors that trigger exocytosis, a protein family called synaptotagmins. Although our understanding of regulated exocytosis is as yet incomplete, the results from the studies of SNAREs, munc18s, and synaptotagmins have provided a molecular anchor for a more complete future description.