Evidence is accumulating for interference of selected endocrine disrupting chemicals (EDC) with the thyroid axis. EDC disturb thyroid hormone (TH) homeostasis leading to developmental defects, hypothyroidism and altered thyroid growth patterns. A rising incidence of papillary thyroid carcinoma (PTC) in several Western countries cannot be definitely accounted for by improved diagnosis or management of thyroid cancer or improved iodine supply. In recent studies, we and others detected, within the thyroid hormone axis, multiple molecular targets of disruption by EDC, which are used in cosmetics, as pesticides or plasticizers or consumed as plant-derived compounds with the diet or with nutritional supplements. Several of these agents exert adverse effects on thyroid growth and function in animal or in vitro cellular models. Major targets are the sodium iodide symporter (NIS), the hemoprotein thyroperoxidase (TPO), the T4 distributor protein transthyretin (TTR), the deiodinases, TH conjugating enzymes and the TR thyroid hormone receptor family. Still prevailing iodine deficiency in many parts of the world predisposes the thyroid gland to adverse effects of endocrine disrupters especially under phases of vulnerability during development and under adaptive challenges during diseases.