Orphan nuclear receptors such as germ cell nuclear factor (GCNF), steroidogenic factor 1 (SF-1) and liver receptor homolog-1 (LRH-1), are emerging as important ovarian factors in regulating female reproduction. Within the ovary, GCNF (NR6A1) expression is restricted to the oocyte, while SF-1 (NR5A1) is expressed only in the somatic cells, such as granulosa, thecal and luteal cells, and interstitial cells. LRH-1 (NR5A2), an orphan receptor closely related to SF-1, is expressed only in the granulosa cells of the follicles and luteal cells within the ovary. Recent studies using conditional knockout strategies to bypass the embryonic lethality of GCNF and SF-1 null mice have uncovered important roles of GCNF and SF-1 in the oocyte and granulosa cells, respectively. In this review, we will summarize the major findings of GCNF and SF-1 in the ovary from the studies of conditional GCNF and SF-1 knockout mice. The potential role of LRH-1 in the ovary is also briefly discussed. Understanding the ovarian functions of these orphan nuclear receptors may lead to the development of new agents for regulation of female fertility and new medicines for the treatment of female idiopathic infertility, premature ovarian failure, polycystic ovarian syndrome and ovarian cancer.