The purpose of this overview is to demonstrate the new complexities that have been revealed in secretory pathways. It is clear that in some areas (e.g. ATP-driven translocators), mechanisms have been conserved between bacteria and higher eukaryotic cells, while certain new processes involve modified secretory routes (e.g. antigen presentation) which will be restricted to eukaryotic cells. It is generally believed that in the evolution of living systems, the development of membrane-delimited compartments was crucial, and that insertion of proteins into membranes allowed more control of the passage of molecules through the membrane. It has been suggested that the first secretory proteins were in fact membrane bound, and extracellular proteolysis was responsible for the release of the first soluble secretory proteins. If so, it is interesting to note that the process still exists today and Pandiella [259-262] has described how the release of the growth factor transforming growth factor-alpha (TGF alpha) from mammalian cells is a case of regulated surface proteolysis. Finally, it is clear to see that as regards secretory pathways, we should keep an open mind as to which routes are utilized and which are not, and indeed, which routes exist and which do not. It appears that if two secretory organelles exist then some protein will be shown to move between them. Even the cytosol can provide a reservoir for secretory proteins or peptides. Perhaps in time S. S. Rothman will be thought of as the Nostradamus of protein secretion.