Premature menopause, that is, menopause – spontaneous or iatrogenic – occurring at or before the age of 40 years, affects sexual identity, sexual function and sexual relationships. The woman's health, wellbeing and achievement of life's goals may be variably impaired. Factors modulating the individual's sexual outcome after premature menopause include: etiological heterogeneity of premature menopause and associated medical and sexual comorbidities; psychosexual vulnerability to premature menopause and associated infertility in survivors of childhood and adolescent cancers; impact of premature menopause on women's sexual identity, sexual function – particularly the biological basis of desire, arousal, orgasm and vaginal receptivity – and sexual relationships; partner-related factors; fertility issues; and preventive/therapeutic measures. Hormone therapy is indicated but long-term safety data are lacking. An interdisciplinary medical and psychosexual approach comprises appropriate counseling, fertility protection, when feasible, individualized hormone therapy and specific psychosexual treatment(s). Further research on fertility protection and the safety of long-term hormone therapy after premature menopause is needed.