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Primary ovarian insufficiency (POI) is defined as a loss of ovarian function before the age of 40. Its prevalence is estimated to be over 1% of the female population. The pathophysiological mechanisms at play involve a large number of genes involved in follicular maturation and activation via the Hippo/PI3K/Akt cell-signaling pathways. Many complications arise from the hypoestrogenic state engendered by POI, particularly cardiovascular, bone, and neuropsychological complications. Fertility is also impaired. Women with POI should be offered hormone replacement therapy, taking into account their contraceptive needs and risk factors. This is the most effective treatment available to date for limiting bone mineral density loss in these patients and improving their quality of life. As regards fertility management, few techniques are currently available. New knowledge in genetics could enable the development of innovative treatments to reactivate ovarian function in patients suffering from POI. High-powered studies will be needed to validate these hypotheses.