Vertebrate reproduction is controlled by 2 pituitary gonadotropin hormones (GtHs), FSH and LH, binding to gonadotropin hormone receptors (GtHRs) in gonadal tissues. All gnathostome vertebrates have been confirmed to possess at least 1 receptor for each GtH [LH receptor (LHR) and FSH receptor (FSHR)], except for species of the reptilian (nonavian sauropsidan) orders, such as lepidosauria, testudines, and crocodylia, which showed inexplicable reactions to heterologous amphibian, avian, and mammalian GtHs in early endocrinological studies. This study investigated the number and function of reptilian GtHRs. Genomic and transcriptomic analyses of selected tetrapod species now strongly suggest the inactivation of the LHR in all nonavian sauropsidans. This gene inactivation likely occurred independently in 3 branches of the sauropdisan clade, sparing only the avian class. Bioassays served to investigate the binding specificity of squamate, chelonian, crocodilian, avian, and mammalian GtHRs with their homologous and heterologous GtHs. The FSHR of a squamate lizard proved completely promiscuous to both its homologous GtHs, while the chelonian FSHR responded slightly stronger to the homologous LH than FSH, and the crocodylian FSHR was only stimulated by the homologous LH but not FSH. We therefore propose a modified paradigm with a neuroendocrine control of nonavian reptilian reproduction by a single GtHR and either 1 GtH in crocodylians or 2 GtHs in chelonians and squamate reptiles. Finally, we discuss hypotheses of tightly regulated temporal and spatial expression of the remaining FSHR in different gonadal somatic cells and temperature-dependent functions of the single nonavian reptilian GtHR.