Progesterone plays a central coordinate role in regulating reproductive events associated with the establishment and maintenance of pregnancy including ovulation, uterine and mammary gland development and tumorigenesis, and neurobehavioral expression associated with sexual responsiveness. The effects of progesterone are mediated by two receptor proteins (PR), termed A and B, that arise from a single gene and act as ligand-activated transcription factors to regulate the expression of reproductive target genes. Null mutation of both proteins in mice leads to pleiotropic reproductive abnormalities. This review summarizes the structure and functional properties of the PR isoforms and how functional differences between these proteins are likely to impact on the overall physiologic role of the receptor in reproductive systems.