Genetically modified mouse models have turned out as fundamental tools to provide new evidence on the role of gonadotropins in reproductive physiology and pathophysiology. We have developed transgenic mice with persistent and ubiquitous production of human chorionic gonadotropin (hCG). Two different lines were generated: mice expressing the hCGβ-subunit and the common α-subunit. Crossbreeding mice harboring the hCGβ-subunit coding sequence (hCGβ+) with those carrying the common α-subunit (hCGα+) produced double transgenics (hCGαβ+), which expresses both subunits in a chronic and ubiquitous fashion. In this way, we were able to amplify certain actions of hCG that otherwise would have remained unnoticed; consequently, multiple reproductive alterations and tumorigenesis were observed in these mice. The purpose of this Chapter is to summarize the main findings of these studies. We will discuss the implications of this hormonal disturbance on the reproductive axis, and the insights they may provide into human health and disease.