Follicle-stimulating hormone (FSH) is a glycoprotein regulating development and reproduction. In both adult fertile males and females, FSH mediates spermatogenesis and folliculogenesis, acting through its G-protein coupled receptor (FSHR). Mutations and single nucleotide polymorphisms occurring within the genes encoding the hormone beta subunit and FSHR may modulate or even impair the physiological function of FSH in both males and females. Synthesis and secretion of FSH are described in the chapter, with a specific overview on the pathways activated upon FSH-FSHR interaction and the physiology of the hormone.