Adrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA-sulphate (DHEA-S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA-S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA-S production, and the cell biology of the adrenal zona reticularis.