The incidence of autoimmune pathologies is increasing worldwide. This has stimulated interest on their 24 etiopathogenesis, caused by a complex interaction of genetic and environmental factors. With the advent 25 of genome-wide linkage, candidate gene and genome wide association studies, risk polymorphisms in 26 autophagy-related genes were discovered in several autoimmune conditions suggesting the possible con-27 tribution of autophagy to their etiopathogenesis. Autophagy represents the principal catabolic process me-28 diated by lysosomes used by eukaryotic cells and is strictly regulated by proteins belonging to the Atg 29 family. The function of autophagy has been well characterized in various tissues and systems, but its role 30 in the regulation of innate and adaptive immune systems has been only recently discovered. It plays a fun-31 damental role in the modulation of thymocyte selection and in the generation of T lymphocyte repertoire by 32 participating in the intracellular antigen presentation on MHC class-II molecules by thymic epithelial cells.33 Furthermore, the generation of mice with knockout for specific autophagy-related genes induced several 34 immunological alterations, including defects in B and T cell compartments and in T cell activation. In this 35 review we report recent evidence on the role of autophagy in autoimmunity and discuss its relevance to 36 the pathogenesis of these diseases. We finally highlight that future research may disclose potential new 37 therapeutic targets for the treatment of this category of disorders by modulating the autophagic pathway.