This chapter focuses on mechanism of action of the principal steroid secretory products of the ovary - namely, estradiol and progesterone. The chapter discusses the involvement of these hormones in the reproductive system and in nonreproductive physiologic systems. Estrogen (E) and progesterone (P) play significant role in both the endocrine and intracrine regulation of all aspects of female reproduction. Together they act at the level of hypothalamus, anterior pituitary, ovary, and uterus to coordinate neuroendocrine pulsatile secretion of gonadotropin releasing hormone, cyclic release of gonadotropins FSH and LH, ovulation, and endometrial development in preparation for implantation and maintenance of fertilized embryos. Both hormones are also essential for pubescent and pregnancy mammary gland development and are involved in the biology of the cardiovascular, immune, central nervous, and skeletal systems. Studies exhibit that both E and P are related to almost all aspects of human physiology leading to a valid basis for optimism that these hormones can successfully address mechanisms of human dysfunction and provide opportunities for development of new therapies as each of these hormones can become targets for manipulation by novel therapeutic interventions.