Because of its ability to cause the release of thyrotropin (TSH), prolactin (PRL), and, under particular circumstances, also of other adenohypopyseal hormones, from the pituitary, thyrotropin-releasing hormone (TRH) has been widely used as a diagnostic tool for about 30 years. The recent introduction of an ultrasensitive TSH assay, able to clearly distinguish suppressed from unsuppressed TSH levels, has tendered the use of the TRH test obsolete in the diagnosis of classic hyperthyroidism. On the contrary, the TRH test is still extremely useful in hyperthyroid patients with inappropriate secretion of thyrotropin, allowing the distinction between TSH-secreting pituitary tumors (usually unresponsive) and the pituitary variant of resistance to thyroid hormone (PRTH) syndrome (always responsive). In hypothyroidism, the TRH test is still of value in patients with preclinical primary hypothyroidism, as they show exaggerated TSH response, and in those with central hypothyroidism, allowing the differentiation between pituitary (secondary) and hypothalamic (tertiary) hypothyroidism. The availability of high-resolution imaging techniques such as magnetic resonance has rendered the use of the TRH test obsolete, to distinguish microprolactionomas from functional hyperprolactinemia. The TRH test still has great clinical value in the follow-up of patients with pituitary tumors (in particular somatotropinomas and clinically nonfunctioning pituitary adenomas) showing abnormal responses of anterior pituitary hormones other than TSH.