In all mammalian species studied, atresia is a prominent feature of ovarian follicular development of all follicles present at birth, more than 99% undergo atresia. The mechanism behind this massive cell death is unknown. Earlier studies have shown that hormones, including gonadotropins and gonadal steroids, modulate the incidence of morphologic atresia. Recently, programmed cell death or apoptosis has been found to be the underlying mechanism of atresia based on the development of quantitative DNA fractionation and in situ assays for detecting internucleosomal DNA fragmentation, a hallmark for apoptosis. With the application of these methods, gonadotropins, estrogens, and several growth factors have been shown to be antiapoptotic hormones, whereas androgens and gonadotropin-releasing hormone are apoptosis-inducing agents in the rat ovary. Although the molecular mechanism for follicle atresia is still unclear, ovarian granulosa cell apoptosis represents an active cell suicide controlled by gonadotropins, gonadal steroids, and several intraovanan factors.