People with disorders of sex development (DSD) may have impaired sex steroid production or their gonads removed before, during or after adolescence, thus requiring hormone replacement therapy (HRT) to induce puberty and/or maintain secondary sexual characteristics, to optimize bone health, and to promote physical and social well-being. Oestrogens are usually used for this purpose in persons reared as females (eventually combined with progestins if a uterus is present) and androgens in those reared as males. An alternative therapy for women with ascertained complete androgen insensitivity syndrome could be testosterone, because this is the main sex steroid hormone secreted by their gonads, but this approach remains to be better explored. Few sound evidence-based data are available to guide HRT administration at puberty and in adulthood in individuals with DSD, but recent data and new formulations may give better perspectives for the future.