The use of gonadotropin-releasing hormone agonists (GnRHa) for prevention of chemotherapy-induced gonadotoxicity remains controversial. With the initial dose of GnRHa, the pituitary gland releases endogenous gonadotropins. This initial follicle stimulating hormone (FSH) release stimulates the ovary. After continued GnRHa exposure, further FSH release is prevented. Gonadotropin-releasing hormone analogues can be administered in many formulations with different durations of action. The most common side effects of GnRH analogues are related to the subsequent estrogen deprivation. Vasomotor symptoms, hot flushes, night sweats, vaginal dryness and headaches can occur. Cotherapy of a GnRHa during chemotherapy has been under investigation since the mid 1990s. If prolonged GnRHa administration decreases ovarian blood flow, then less chemotherapy may reach the ovary. Direct effects of GnRHa or FSH on ovarian tissue may influence ovarian response to chemotherapy. For GnRHa to be of benefit to fertility preservation, they would likely need to spare both oocyte quantity and quality.