This mini review summarizes the current knowledge of the hypothalamic-pituitary-thyroid (HPT) endocrine system in lampreys, jawless vertebrates. Lampreys and hagfish are the only two extant members of the class of agnathans, the oldest lineage of vertebrates. The high conservation of the hypothalamic-pituitary-gonadal (HPG) axis in lampreys makes the lamprey model highly appropriate for comparative and evolutionary analyses. However, there are still many unknown questions concerning the hypothalamic-pituitary (HP) axis in its regulation of thyroid activities in lampreys. As an example, the hypothalamic and pituitary hormone(s) that regulate the HPT axis have not been confirmed and/or characterized. Similar to gnathostomes (jawed vertebrates), lampreys produce thyroxine (T4) and triiodothyronine (T3) from thyroid follicles that are suggested to be involved in larval development, metamorphosis, and reproduction. The existing data provide evidence of a primitive, overlapping yet functional HPG and HPT endocrine system in lamprey. We hypothesize that lampreys are in an evolutionary intermediate stage of hypothalamic-pituitary development, leading to the emergence of the highly specialized HPG and HPT endocrine axes in jawed vertebrates. Study of the ancient lineage of jawless vertebrates, the agnathans, is key to understanding the origins of the neuroendocrine system in vertebrates.