This chapter synthesizes our understanding of HPG regulation of reproduction in teleosts and includes a section on environmental cues and endocrine disruption. Regulation of the physiology of maturation, spawning, and gonadal differentiation, primarily by the hypothalamo-pituitary-gonadal (HPG) system, allows fishes to be reproductively successful under a variety of conditions. Fishes have two distinct gonadotropic cell types; combined with direct hypothalamic innervation, this simplifies differential regulation of the gonadotropins by gonadotropin-releasing hormone. The nuclear steroid receptors in fishes are well characterized concerning their expression patterns and ligand binding properties. Fishes have an extraordinary degree of interaction between genetic sex and temperature. Anthropogenic sources of compounds capable of interacting with the HPG axis in fishes are a modern environmental challenge. The reproductive endocrine system controls reproduction in fishes for times most beneficial for spawning and offspring survival.