The rôle of secretion and membrane fusion in health and disease is profound. The pioneering discoveries by Jena and Rothman of a new cellular structure, the porosome, have essentially explained this process. The elucidation of the porosome’s morphology, composition and functional reconstitution in lipid membranes explain how cellular products destined for secretion undergo maturation by shuttling between subcellular compartments via budding and fusion of transport vesicles. Finally packaged in membranous sacs called secretory vesicles, which fuse at specific plasma membrane locations, they expel their contents. These and some other aspects of the discoveries of these scientists are described.