A renaissance in the autophagy field has illuminated many areas of biology, and infectious disease is no exception. By identifying key components of this broadly conserved membrane traffic pathway, yeast geneticists generated tools for microbiologists and immunologists to explore whether autophagy contributes to host defenses. As a result, autophagy is now recognized to be another barrier confronted by microbes that invade eukaryotic cells. Mounting evidence also indicates that autophagy equips cells to deliver cytosolic Ags to the MHC class II pathway. By applying knowledge of the autophagy machinery and exploiting microbes as genetic probes, experimentalists can now examine in detail how this ancient membrane traffic pathway contributes to these and other mechanisms critical for infection and immunity.