Novel progesterone receptor modulators (PRMs) have recently been demonstrated to be effective in the treatment of patients with symptomatic uterine leiomyomata. PRMs are shown to reduce leiomyoma size and improve leiomyoma-associated symptoms. However, the precise mechanisms underlying the action of PRMs remain to be elucidated. My co-workers and I have investigated in vitro action of PRMs in cultured leiomyoma cells and revealed that PRMs inhibit cell proliferation and induce apoptosis of leiomyoma cells. Moreover, our recent studies show that PRMs can modulate the metabolism of extracellular matrix proteins in cultured leiomyoma cells toward the collagenolysis. The update about an action of PRMs in uterine leiomyoma cells in vitro is described in this article.