Premature ovarian failure is the term usually used to describe women aged younger than 40 years who present with amenorrhea, hypergonadotropinism, and hypoestrogenism. Such women may ovulate and even conceive after the diagnosis is made, so it may be more appropriate to refer to these patients as having “primary ovarian insufficiency,” or alternatively, as having “hypergonadotropic hypogonadism” or “primary hypogonadism.” The clinical presentation is diverse, and several different disorders can lead to premature ovarian failure. Affected women should be investigated for premutations of the FMR1 gene (causing fragile X syndrome in its fullest form) and for adrenal antibodies. Thyroiditis is the most frequent autoimmune disorder associated with premature ovarian failure and should be ruled out as well. Osteopenia is increased in women with premature ovarian failure, and measures to prevent accelerated bone loss are warranted. Hormone therapy (HT) should be provided to eliminate symptoms of estrogen deficiency and help prevent osteopenia, but will not necessarily (and inexplicably) prevent pregnancy in the 5–10% of women who conceive spontaneously after the diagnosis is made. There are no data indicating that these young women are at increased risk of side effects from HT. If pregnancy is desired, use of donor oocytes with in vitro fertilization is most likely to result in pregnancy.