A potential consequence of chemotherapy is the destruction of oocytes, resulting in primary ovarian insufficiency (POI) in young patients; this often results in secondary amenorrhea and necessitates hormone replacement therapy. Regardless of the etiology of POI, the chance of pregnancy is low in this patient population. Given the extent to which oocyte depletion or dysfunction is variable, there is the possibility of spontaneous ovulation on hormone replacement therapy and subsequent pregnancy, however. If pregnancy is not desired, contraception always should be discussed. In most patients, the etiology of POI will not be known, but the treatment for all patients includes estrogen and progesterone therapy, which ensures the development of secondary sex characteristics, acquisition of peak bone mass, and promotion of uterine growth and maturation. Early diagnosis, patient education, and emotional support are important to mitigate long-term sequelae.