This Review synthesizes evidence that RAGE hyperactivation, during the process of ovarian aging, disrupts folliculogenesis, granulosa cell function and steroidogenesis via MAPK-ERK, PI3K-AKT-mTOR and NF-κB pathways, exacerbating conditions such as premature ovarian failure, polycystic ovary syndrome and ovarian cancer. Here, NFKB1 is linked to ovarian cancer.