The mammalian ovary consists of a large number of dormant immature follicles, each containing a single oocyte and located on the periphery of the ovary. With each reproductive cycle, a group of immature follicles is sequentially activated to resume growth, and pituitary gonadotropins and ovarian steroid and peptide hormones cooperate to ensure further growth and development. A single dominant follicle eventually emerges, ovulates, and then involutes to allow the selection of the next group of follicles. While hormones are known to control the later stages of folliculogenesis, little is known about the pathways that activate individual immature primordial follicles in the dormant follicle pool. We advance a new hypothesis: that follicle activation is dependent on the physical environment of the ovary in addition to well-established hormonal cues. This novel perspective on ovarian function may provide new avenues to study follicle dynamics and identify therapeutic targets for ovarian dysfunction.