Estetrol is a steroid produced by fetal liver. It was discovered over 40 years ago. At that time it was examined as a marker of high-risk pregnancy. The research was terminated as estetrol proved to be of limited use in this setting. In recent years interest in estetrol has renewed as it was shown to have qualities similar to SERM. In pre-clinical and phase II clinical trials it has been evaluated in alleviating the symptoms of menopause, prophylaxis of osteoporosis, prophylaxis and treatment of breast cancer and as an E component of combined oral contraceptives. Despite promising results further investigation is necessary to fully assess the clinical role of estetrol.