Estrogen acts as agonist on the estrogen receptor. The effects of estrogen may be confounded by concomitant treatment with progestins. Postmenopausal hormone therapy (HT) can be divided into: postmenopausal estrogen therapy (ET - estrogen alone), and postmenopausal estrogen-progestin therapy (EPT – estrogen plus a progestin). EPT is associated with an increased risk of cardiovascular disease, cerebrovascular disease, and breast cancer. ET is not associated with a significant increase in any of these. Both EPT and ET are associated with an increase in venous thromboembolism. Both EPT and ET reduce the risk of vertebral and overall fracture risk. At present use of EPT or ET should be limited to short-term treatment of severe menopausal symptoms. This review discusses the effects and side effects of EPT and ET and potential ways of avoiding some of the side effects.