Exocytosis is initiated within a highly localized region of contact between two biological membranes. Small areas of these membranes draw close, molecules on the two surfaces interact, and structural transformations take place. Membrane fusion requires the action of proteins specialized for this task, and these proteins act as a fusion machine. At a critical point in this process, a fusion pore forms within the membrane contact site and then expands as the spherical vesicle merges with the flat target membrane. Hence, the operation of a fusion machine must be realized through the formation and expansion of a fusion pore. Delineating the relation between the fusion machine and the fusion pore thus emerges as a central goal in elucidating the mechanisms of membrane fusion. We summarize present knowledge of fusion machines and fusion pores studied in vitro, in neurons, and in neuroendocrine cells, and synthesize this knowledge into some specific and detailed hypotheses for exocytosis.