Following the discovery of coactivators for nuclear receptors and the identification of a significant number of progesterone receptor (PR) target genes, our understanding of PR action has extended from its normally recognized functions to a wide variety of seemingly unlinked biological processes. Recent advances in defining the action of PR coactivators has revealed important mechanisms involving multiple layers of regulation in PR-mediated transcription. In this review, we will discuss the current understanding of PR physiology and the molecular basis of coactivator function in PR signaling events.