Intracellular degradation by autophagy plays a role in the maintenance of cellular homeostasis under normal conditions and during periods of cellular stress. Autophagy has also been implicated in several other cellular processes including immune recognition and responsiveness. More specifically, autophagy has been identified as a route by which cytoplasmic and nuclear Ag are delivered to MHC class II molecules for presentation to CD4(+) T cells. Autophagy has also recently been implicated in MHC class I cross-presentation of tumor Ag and the activation of CD8(+) T cells. This review discusses the role of autophagy in modulating MHC class I and class II Ag presentation as well as its implication in regulating autoimmunity and tolerance, tumor immunity, and host defense against intracellular pathogens.