Thyrotropin releasing hormone (TRH: pyroglutamic acid-histidine-prolineamide) regulates the activity of cells in the anterior pituitary and within the central and peripheral nervous systems. TRH, which has been the subject of much research over the past three decades, exerts its effects by acting through class A G-protein coupled receptors. The recent discovery of a second receptor subtype has generated an interest in the discovery of receptor subtype-selective TRH analogs. In this review, we describe advances in the development of TRH analogs and in the understanding of their mechanism of interaction with TRH receptors. We also describe the recent breakthrough in the identification of analogs that bind selectively at TRH-R2.