Autophagy is a mechanism by which eukaryotic cells degrade cytosolic components, targeting them for degradation via the formation of unique double-membraned vesicles that then enter the endosomal/lysosomal pathway. Autophagy is recently appreciated to be an important component of the innate immune response in both vertebrates and invertebrates, directly destroying many intracellular pathogens. With this in mind, compounds that stimulate autophagy promise to be valuable immunomodulatory therapeutics for a wide variety of infections. However, some pathogens, including several RNA viruses, appear to subvert the autophagy pathway to facilitate their replication and, possibly, intercellular spread. For these pathogens, inhibitors of autophagy could be very valuable therapeutics. For these scenarios to become reality, a basic understanding of how the autophagy pathway can, in some cases, clear infections while promoting others would be highly valuable.