Premature ovarian insufficiency (POI) is defined as amenorrhea for 6 months and is associated with elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels due to failure of the ovaries. Early menopause is when this occurs in women under 45 years of age. The term POI is used rather than premature ovarian failure (POF) as resumption of function occurs in a small proportion of women. The exception to this is if the ovaries are absent or removed surgically. This chapter describes the etiology and diagnosis of POI. The etiology includes following as genetic, iatrogenic, autoimmune disorders, and environmental toxins.