Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and thyrotropin receptor (TSHR) is increased by genetic polymorphisms, a high number of antigenic peptides available for binding to human leukocyte antigen (HLA), and a high degree of glycosylation. Antigens bound to HLA are presented by antigen-presenting cells to T cell receptors. Further interaction between both cells is required via binding of CD40 ligand to CD40 and of B7-1/2 to CD28 for activation of T cells. Complex regulatory mechanisms serve to prevent an immune response directed against 'self'-antigens in the thymus (central tolerance) and in peripheral tissues (peripheral tolerance) with the help of regulatory T cells. Breakdown of tolerance to thyroid antigens can result in thyroid autoimmunity, which may happen in subjects who have the wrong genes and who are exposed to the wrong environment. Polymorphisms in thyroid genes (TG, TSHR) and immunoregulatory genes (HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, FOXP3) would contribute for about 70% to AITD, and environmental exposures (like iodine, smoking, infections, parity) for the remaining 30%. Thyroid-infiltrating activated T cells may lead to cell-mediated immunity, thyroid injury and eventually hypothyroidism, whereas humoral immunity via TSHR-stimulating antibodies may give rise to hyperthyroidism. Pediatric Hashimoto's and Graves' disease are less prevalent than in adults, and the female preponderance is also less marked in children. The discrepancy is probably due to relatively less involvement of environmental insults in children, whereas the prevalence of risk alleles in AITD children is higher than in AITD adults.