Autophagy is a complex cellular process that involves dynamic membrane rearrangements under a range of physiological conditions. It is a highly regulated process that plays a role in cellular maintenance and development, and has been implicated in a number of genetic diseases. Upon induction of autophagy, cytoplasm is sequestered into vesicles and delivered to a degradative organelle, the vacuole in yeast or the lysosome in mammalian cells. The process is unique in that it converts material that is topologically intracellular into topologically extracellular. Autophagy was first described more than 50 years ago, but it is since the discovery of the pathway in yeast cells that our knowledge about the molecular events taking place during the process has expanded. The generation of autophagy-specific mutants in a variety of yeast cell lines has provided insight into functional roles of more than 15 novel genes, double that number if we include genes whose products function also in other processes. Although we have learned much about autophagy, many questions remain to be answered. This review highlights the most recent advances in the autophagy field in both yeast and mammalian cells.