FSH (follicle-stimulating hormone) is a master endocrine regulator of somatic cells of the gonads that support gametogenesis. In the male, FSH dictates the Sertoli cell proliferation rate prior to puberty, then maintains their main biological roles as nurturing cells and physical support to spermatogenesis throughout life. In the female, FSH is instrumental in processing the terminal differentiation phase of folliculogenesis that progressively drives the ovarian follicle to ovulation. The biological function of FSH is transduced by a membrane receptor, the FSH receptor (FSHR). Deciphering the molecular bases of the developmental switch in FSH biological activities is required to gain insights into FSH-induced signaling pathways. This quest has led to the identification of a complex interconnected signaling network affected by testicular paracrine factors, implying not only protein post-translational modifications but also regulation by microRNA and chromatin remodeling. In the female, the emphasis is now placed on deciphering the complex functional relationships between the LHCGR (luteinizing hormone/choriogonadotropin hormone receptor) and the FSHR that trigger intertwined signaling networks in the same granulosa cell type. Breakthroughs in the organization and dynamic functioning of the FSH-induced signaling network are expected to identifying novel regulatory processes and therapeutic strategies for infertilities and contraception.