This review discusses mechanisms by which progesterone receptors (PR) regulate transcription. We examine available data in different species and tissues regarding: (1) regulation of PR levels; and (2) expression profiling of progestin-regulated genes by total PRs, or their PRA and PRB isoforms. (3) We address current views about the composition of progesterone response elements, and postulate that PR monomers acting through “half-site” elements are common, entailing cooperativity with neighboring DNA-bound transcription factors. (4) We summarize transcription data for multiple progestin-regulated promoters as directed by total PR, or PRA vs. PRB. We conclude that current models and methods used to study PR function are problematical, and recommend that future work employ cells and receptors appropriate to the species, focusing on analyses of the effects of endogenous receptors targeting endogenous genes in native chromatin.