Premature ovarian failure, also known as primary ovarian insufficiency (POI), is a clinical syndrome defined by the loss of ovarian function before the age of 40. The current criteria for a POI diagnosis include irregularities in the menstrual cycle lasting for at least 4 months and two recordings of FSH serum concentrations whose values are in postmenopausal ranges, measured at least 1 month apart. The prevalence of POI is 1% in women before the age of 40. The etiology consists of spontaneous, iatrogenic and idiopathic POI. The most common, known causes are chromosomal and genetic abnormalities, autoimmunity, aggressive gynecologic surgeries, chemotherapy and radiotherapy. However, in 90% of the cases, the etiology is unknown, and these women are diagnosed with idiopathic POI. POI occurs through two major mechanisms: follicle dysfunction and follicle depletion. Regardless of the etiological mechanism, POI has life-long implications on physical and mental health. Untreated POI is associated with higher incidence of cardiovascular diseases and lower bone mineral density (BMD), which is associated with higher risk of fractures. Thus, timely diagnosis and early initiation of hormone replacement therapy are crucial. Also, infertility in women who suffer from POI has a negative impact on life quality - since the chances of spontaneous conception are low, either assisted conception by using donor oocyte or adoption are recommended. The key strategy in preserving future fertility for women who may be at risk for POI involves cryopreservation of oocytes, embryos, or ovarian tissue. Primarily though, female patients suffering from POI need to be provided with psychological support.