Lampreys and hagfish of the class Agnatha are of particular importance in understanding endocrinological relationships since they represent the oldest lineages of extant vertebrates which evolved over 550 million years ago. This review briefly summarizes the latest findings on the reproductive endocrinology of the sea lampreys. Since the First International Symposium of Fish Endocrinology in 1988, when virtually little was known of the hypothalamic-pituitary-gonadal axis, substantial new biochemical, molecular, physiological and immunological evidence has now clearly shown that lamprey reproduction is controlled by the neuroendocrine axis. In addition, five brain and six pituitary hormones of lampreys have been identified mainly by Sower and Kawauchi and colleagues between 1986 and 2000. We now hypothesize that lamprey reproduction is a highly synchronized process that is initiated or mediated by a coordination of complex integration of environmental cues and hormonal mechanisms which is broadly similar to that exhibited by gnathostome vertebrates.