The hormonal interactions in the hypothalamic–pituitary–gonadal (HPG) axis form the backbone of the endocrine regulation of reproduction. Unlike the stable function of most organ systems throughout life, the function of the HPG axis undergoes dramatic qualitative and quantitative changes at the different stages of life and continues to show very dynamic changes in adult female life to ensure monthly ovulation of a single oocyte and subsequent readiness for pregnancy. The purpose of this chapter is to describe the normal and pathological development, maturation, mature function, and senescence of the human HPG axis.