The major target organ of progesterone is the reproductive system. Progesterone, in association with estrogen, is involved in the development and sexual maturation of the reproductive organs and orchestrates the menstrual cycle. Progesterone takes part in all the processes from the preparation of the uterine decidua, myometrium and cervix during the menstrual cycle through blastocyst implantation and is the key hormone in pregnancy maintenance, sustaining of myometrial quiescence, cervical competence and modulation of the maternal immune system during pregnancy. Accumulating evidence suggests that, in humans, progesterone withdrawal during parturition is probably functional and involves a shift in the balance between progesterone and cortisol, as well as changes in the genomic and non-genomic effects of progesterone in the cellular level. This chapter describes the specific effects of progesterone on the uterus and the cervix during the normal menstrual cycle, and in maintenance of normal pregnancy, and during parturition. Progesterone also has numerous systemic effects and influences other organs outside the female reproductive tract.