The main cause of endemic goiter is iodine deficiency. For the last four decades, it has been thought that the reason for goiter development is the increased action of thyreotropin (TSH) on thyroid cell proliferation. During the last years, however, it became evident that local growth factors may be more directly involved in goiter formation and, furthermore, iodinated derivatives of membrane lipids are modulators of this growth factor's actions. TSH modulates both, the growth factor and growth factor receptor expression as well as the iodine content of the thyroid gland. In addition, most of the effects of TSH on thyroid volume seems to be the induction of thyroid hypertrophy, but not hyperplasia which is related to the action of local growth factors. These new insights in the pathophysiology of goiter development are important for the regimen of endemic goiter therapy. The current concept of goiter treatment by a TSH suppressive therapy has been derived from the previous hypothesis that TSH alone is more effective in causal goiter treatment than the TSH suppressive therapy.