The corpus luteum is a transient endocrine gland that produces essentially progesterone, a required product for the establishment and maintenance of early pregnancy. In the absence of pregnancy, the corpus luteum will cease to produce progesterone, and the structure itself will regress in size over time. The life span and function of the corpus luteum is regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. Although the process of luteal formation and regression has been studied for several decades, many of the regulatory mechanisms involved in loss of function and involution of the structure are incompletely understood. In rodents, prolactin is the major luteotrophic hormone by maintaining the structural and functional integrity of the corpus luteum for several days after mating. Other factors involved in steroidogenesis, control of cell cycle, apoptosis, and tissue remodeling have been shown to play a role in corpus luteum development and maintenance. Especially, PGF2alpha seems to be the most potent luteolytic hormone. One of the most important advances in the study of mammalian genes has been the development of techniques to obtain defined mutations in mice. These tools enable us to target specific genes and to analyze the impact of their loss on cell fate and function. With these approaches, several receptors, transcription factors, enzymes, and other factors have been linked to corpus luteum development and maintenance. These models are helping to define mechanisms of reproductive function and to identify potential new contraceptive targets and genes involved in the pathophysiology of reproductive disorders.