Pituitary autoimmunity, considered a synonym of autoimmune hypophysitis, defines a wide spectrum of conditions (neoplastic, functional, and iatrogenic pituitary disorders; and extra-pituitary autoimmune and non-autoimmune diseases), and is characterized by the presence of antipituitary antibodies (APAs) at various titer and prevalence. These conditions have been increasingly recognized not only in adults, but also in children. The autoimmune pathogenesis, histological features of the primary (i.e. lymphocytic, granulomatous, xanthomatous, IgG-4 related lymphoplasmacytic, and necrotizing) forms, and the pathognomonic association of lymphocytic hypophysitis with pregnancy and CTLA-4 antibody therapy, have been clearly demonstrated. Meanwhile, non-invasive differential diagnosis remains extremely challenging since none of the suggested clinical, radiological or laboratory criteria are pathognomonic. In this context, the demonstration of APA is not sufficient, because of the lack of specificity, and associated methodological and theoretical issues (i.e. disease marker vs. pathogen; antigen target(s); and diagnostic/prognostic significance). This chapter aims at providing a comprehensive overview of the pituitary autoimmunity panorama for epidemiological, clinical radiological, and histological aspects, while discussing the main diagnostic limitations and issues associated with disease management.