A partial answer to this question may be related to the fact that autophagy (used as the synonym of macroautophagy in this article) has been discovered1 and described by electron microscopy (see refs. 2-4 for a review of the early literature). Electron microscopy is still an indispensible method for studying this process. Starting in the 1990s, the unicellular yeast with its relatively big vacuole proved to be uniquely suited to study autophagy by light microscopy (with supporting studies by the electron microscope). A similar approach for multicellular animals, however, seemed and still seems to be unworkable. However, the new era had already begun with the discovery of autophagy genes in yeast (see chapters 6 and 7) and the challenge was there to look for a genetically tractable metazoan organism.