The autoimmune polyglandular syndrome (APS) represents a group of complexdisorders of immune dysregulation that leads to autoimmunity and development of atleast two different endocrine or non-endocrine abnormalities. According to aetiologyand pathogenesis, APS can present with three distinct phenotypes: APS type 1, APStype 2 and IPEX (immune dysfunction, polyendocrinopathy, enteropathy, X-linked)syndrome. Both, APS type 1 and IPEX syndrome are monogenic disorders thatdevelop in infancy or early childhood, while APS type 2 is a complex polygenicdisorder that usually presents later, in adolescence or adulthood. Clinical presentationcan be acute such as in diabetes mellitus, symptomatic and slow-progressive such asin adrenocortical insufficiency or even asymptomatic such as in celiac disease.Autoantibodies precede tissue destruction, and measurement of these autoantibodiescan be used to identify risk of subsequent tissue insufficiency. The diagnosis is often challenging, mainly due to rarity of condition, variability of theearly clinical picture and frequently insidious course of disease. Therefore, wheneverone organ-specific autoimmune disorder is diagnosed important to always have a highindex of suspicion for possible APS. Early diagnosis permits active screening forprogressive tissue damage, while early initiation of treatment prevents acute and long-term complications.